Sections

Overview

Practice Essentials

Chorioamnionitis (also known as "triple I": intrauterine inflammation or infection or both) is a complication of pregnancy caused by bacterial infection or inflammation of the fetal amnion and chorion membranes.

Signs and symptoms

The characteristic clinical signs and symptoms of chorioamnionitis include the following:

Maternal fever (intrapartum temperature >100.4°F or >38.0°C).^[1]Other observed signs include the following^[2]:
Baseline fetal tachycardia (>160 beats per min for 10 min or longer, excluding accelerations, decelerations, and periods of marked variability)
Maternal leukocytosis (total blood leukocyte count >15,000 cells/μL) in the absence of corticosteroids
Definite purulent fluid from the cervical os
Other nonspecific signs such as maternal tachycardia and uterine tenderness are deemphasized by a report from a workshop conducted by the National Institute of Child Health and Human Development (NICHD).^[2]

The NICHD workshop recommended using the term “triple I” to address the heterogeneity of this disorder. The term "triple I" refers to intrauterine infection or inflammation or both, and it is defined by strict diagnostic criteria (see below); however, this terminology has not been universally accepted.^[3]It is important to differentiate between clinical and histologic chorioamnionitis; the latter tend to be “silent” and present only with preterm labor or preterm premature rupture of membranes (PPROM). The risk of neonatal sepsis is increased when chorioamnionitis is diagnosed in the laboring mother; however, the risk is much lower than anticipated based on historical figures when widespread use of intrapartum antibiotics was not a common practice.^[4]

See Presentation for more detail.

Diagnosis

The diagnosis of clinical chorioamnionitis in pregnancy is commonly made based on clinical findings of fever plus fetal tachycardia, maternal leukocytosis, or purulent fluid coming from the cervical os. Additionally, the pregnant woman with chorioamnionitis may appear ill, even toxic, and she may exhibit hypotension, diaphoresis, and/or cool or clammy skin. However, especially when dealing with histologic chorioamnionitis, maternal clinical signs or symptoms of infection may be absent (silent chorioamnionitis).^[5]

Furthermore, clinical signs and symptoms of chorioamnionitis are not always associated with placental evidence of inflammation.^[6]This is particularly true if maternal fever is the sole criterion for the diagnosis.

Examination for suspected sepsis in the neonate of a mother with chorioamnionitis often yields nonspecific and subtle findings, which may include the following:

Behavioral abnormalities (eg, lethargy, hypotonia, weak cry, poor suck)
Pulmonary: Tachypnea, respiratory distress, cyanosis, pulmonary hemorrhage, and/or apnea
Cardiovascular: Tachycardia, hypotension, prolonged capillary refill time, cool and clammy skin, pale or mottled appearance, and/or oliguria
Gastrointestinal: Abdominal distention, vomiting, diarrhea, and/or bloody stools
Central nervous system: Thermal regulatory abnormalities, behavioral abnormalities, apnea, and/or seizures
Hematologic and/or hepatic: Pallor, petechiae or purpura, and overt bleeding

Laboratory tests

During the intrapartum period, the diagnosis of chorioamnionitis is usually based on clinical criteria, particularly for pregnancies at term.

Laboratory studies for asymptomatic pregnant mothers who present with premature labor or PROM include the following:

Examination of amniotic fluid
Maternal blood studies
Maternal urine studies
Maternal group B streptococcal (GBS) screening test

Testing in febrile pregnant women with suspected chorioamnionitis may include the following:

White blood cell (WBC) counts
C-reactive protein (CRP) levels
Alpha1-proteinase inhibitor (A1PI) complex measurement
Serum interleukin-6 (IL-6) or ferritin levels

Studies to evaluate amniotic fluid and urogenital secretions may include the following:

Bacterial cultures
Leukocyte count
Gram staining
pH
Glucose concentration
Leukocyte esterase activity^[7]
Endotoxin, lactoferrin, and/or cytokine levels (especially IL-6)
Polymerase chain reaction (PCR) for specific microorganisms
Fetal fibronectin, insulinlike growth factor binding protein-1 (IGFBP-1), and sialidase levels
Proteomic profiling^[8]

The criterion standard for diagnosing early-onset bacteremia, pneumonia, or meningitis in neonates is the growth of bacteria in an appropriate specimen (ie, blood, tracheal secretions, cerebrospinal fluid). Screening tests for neonatal sepsis include WBC profiles and CRP determinations.

Other tests that may be used to diagnose early-onset neonatal sepsis include the following:

Serum IL-6 or other cytokine levels
Procalcitonin levels^{[9, 10]}
Serum amyloid A measurements^[10]

Imaging studies

Before the fetus is viable, vaginal ultrasonography can be used to identify women with a shortened cervical canal. A shortened cervical canal is associated with a higher risk of preterm delivery.^{[11, 12, 13]}

Ultrasonography may also be used to ascertain fetal well-being, utilizing the biophysical profile (BPP).

Procedures

Procedures that may be used to evaluate suspected chorioamnionitis or neonatal early-onset sepsis (EOS) include the following:

Needle aspiration and analysis of amniotic fluid, with ultrasonographic guidance: Can confirm the diagnosis of acute chorioamnionitis
Gross/microscopic examination of placenta, fetal membranes, umbilical cord^[14]
Complete blood cell (CBC) count and inflammatory biomarkers, blood culture, and chest x-ray
Controversial: Lumbar puncture of neonates

See Workup for more detail.

Management

Therapy for the mother and/or neonate with chorioamnionitis includes early delivery, supportive care, and antibiotic administration.

Pharmacotherapy

Antibiotic agents used in the treatment of chorioamnionitis include the following:

Ampicillin and gentamicin
Clindamycin or metronidazole when endometritis is suspected (postdelivery)
Vancomycin for penicillin-allergic patients
Alternatives: Monotherapy with ampicillin-sulbactam, ticarcillin-clavulanate, cefoxitin, cefotetan, or piperacillin-tazobactam
Penicillin G: Used exclusively for GBS intrapartum prophylaxis; if intraamniotic infection is suspected, broaden the antibiotic coverage.

Nonpharmacotherapy

Supportive care of the septic neonate may include the following:

Warmth, monitoring of vital signs
Preparedness to perform a full resuscitation, including intubation, providing positive-pressure ventilation
Treatment of hypovolemia, shock, and respiratory and/or metabolic acidosis
Surfactant replacement therapy
Glucose homeostasis
Assessment and treatment of thrombocytopenia and coagulopathy, if present

Surgical option

Cesarean section may be indicated to expedite the delivery.

Although surgical intervention in the newborn is infrequently required in early-onset bacterial infections of the neonate, conditions that may require such intervention include the following:

Epidural or brain abscess
Subcutaneous abscesses
Infections localized to the pleural space
Certain intraabdominal infections (especially if intestinal perforation is present)
Bone or joint infections

See Treatment and Medication for more detail.

Background

Maternal fever during labor, and perhaps other signs and symptoms of chorioamnionitis, often results in a call to the family practitioner, pediatrician, or neonatologist related to concern for the neonate. This communication often causes an evaluation to rule out early-onset neonatal sepsis.^[15]Because of a concern for early-onset sepsis (EOS) when signs and symptoms of maternal chorioamnionitis occur, 18-38 newborns are evaluated and treated with antibiotics for every infant with proven bacteremia. The reason for this clinical phenomenon is that newborns who develop EOS, defined as proven infection (positive culture from a normally sterile site like blood, tracheal aspirate, cerebrospinal fluid) at less than 72 hours of life, have a high mortality rate. A strong association is observed between very preterm infants dying when younger than 24 hours and chorioamnionitis.^{[16, 17]}

Heightened clinical evaluations for EOS began in the 1970s because group B streptococcal (GBS) infections resulted in a neonatal mortality of about 50%.^[18]Over the past 50 years, awareness of GBS-related neonatal morbidity and mortality resulted in the widespread implementation of intrapartum chemoprophylaxis with antibiotics to reduce the risk of GBS disease, which led to an 85% reduction in the rate of culture-proven early-onset GBS sepsis, from approximately1.8 per 1000 live births in the early 1990s to fewer than 0.26 per 1000 live births in 2010.^[19]

Early-onset bacterial infections in the newborn may occur when the mother has abnormal bacterial colonization of the urogenital tract, an ascending but silent amniotic fluid infection, or symptomatic chorioamnionitis. Thus, the physician cannot assume that maternal signs and symptoms alone will identify all infected infants.

GBS infections continues to be the major cause of EOS in term neonates; however, Escherichia coli has surpassed GBS as the most significant pathogen in preterm infants for over 10 years.^[20]Intrapartum ampicillin exposure (as part of GBS prophylaxis as used at some institutions) was identified as an independent risk factor for ampicillin-resistant E coli EOS, as well as for a significant increase in E coli late-onset sepsis.^[21]

Additionally, methicillin-resistant Staphylococcus aureus (MRSA), already a common cause of nosocomial infection in maternity and neonatal units, looms as a potential cause of EOS.^[22]So far, maternal colonization during pregnancy with MRSA has not translated into an increase in MRSA-associated EOS, but close monitoring for this infection is warranted.^[23]

This article discusses intraamniotic infection during pregnancy and its effects on the fetus and newborn, as well as summarizes the history, physical examination, and laboratory findings in both mother and infant to provide appropriate decision-making tools for cost-effective management of the neonate. The subject is expansive in scope, and readers are encouraged to seek more information from other sources. Other Medscape Drugs and Diseases articles of interest include Congenital Pneumonia; Meningitis, Bacterial; and Neonatal Sepsis.

An entire 2016 issue of the Journal of Perinatal Medicine was devoted to clinical chorioamnionitis.^[24] Several chapters in the monograph by Romero et al contain information on the intraamniotic inflammatory response in women with clinical chorioamnionitis, molecular mechanisms to identify infecting microorganisms, and the cytokine profiles of the mother and the newborn infant.^{[25, 26, 27, 28, 29]}

Readers are also referred to the 2017 Committee Opinion Number 712 by the American College of Obstetrics and Gynecology (ACOG) on intrapartum management of intraamniotic infection,^[30]as well as an excellent 2016 review article about clinical chorioamnionitis by Kim et al in the American Journal of Obstetrics and Gynecology that discusses the definition, pathogenesis, grading, staging, and clinical significance of the most common lesions in placental disease, accompanied by illustrations of the lesions as well as diagrams.^[31]

Pathophysiology

Abnormal bacterial colonization of the distal colon during pregnancy may create an abnormal vaginal and cervical microbial environment.^[32]Ascending of cervical and vaginal flora through the cervical canal is the most common pathway to chorioamnionitis. Uncommonly, chorioamnionitis may occur via hematogenous spread as a result of maternal bacteremia (eg, Listeria monocytogenes), or via contamination of the amniotic cavity as a result of an invasive procedure (eg, amniocentesis, fetoscopy). Although spread of peritoneal infection to the amniotic cavity via the fallopian tubes has also been suggested, it is very unlikely.^[31]Subsequent activation of the maternal and fetal inflammatory response systems generally lead to labor and/or rupture of membranes.^[33]More than 3 decades ago, rectovaginal colonization with group B Streptococcus (GBS) during pregnancy was found to be associated with GBS-related infection of the fetus or newborn.^[18]Studies have demonstrated that other types of bacteria residing in the vagina, cervix, or both ascend through intact or ruptured fetal membranes and initiate amniotic fluid infection, chorioamnionitis (inflammation), or both.^[34]

Urinary tract infection during pregnancy can bathe the vagina with bacterial pathogens and is a recognized risk factor for neonatal sepsis.^[35] This observation is particularly true for untreated asymptomatic GBS-related bacteriuria.^[36]

Bacterial vaginosis is associated with premature labor, although overt infection of the neonate with microbes causing bacterial vaginosis is uncommon. Screening for and treatment of bacterial vaginosis and other genital infections may prevent preterm birth, especially if initiated before 20 weeks' gestation.^[37]

Many associations related to infection and preterm birth have been made; however, the mechanisms of these relationships are not necessarily understood. These associations include periodontitis,^[38] blood types A and O,^[39]alcoholism,^[39] and obesity during pregnancy.^[40]

In the mid-trimester of pregnancy (14-24 weeks), ultrasonographic evidence of a short cervix may be the only clinical finding in intraamniotic fluid infection.^[11]Cervical insufficiency, regardless of bacterial culture results from amniotic fluid, is associated with intraamniotic inflammation, preterm birth, and other adverse outcomes of pregnancy.^{[41, 42]}Related issues to cervical insufficiency are mechanical methods of cervical ripening that are also suspected of increasing maternal and neonatal infections.^[43]A Cochrane review stated that vaginal prostaglandin to initiate labor after premature rupture of membranes may increase maternal and fetal infection and warrants more research.^[44]Each of these factors may be associated with altered host defenses that allow ascending infection from the urogenital tract to placental tissues and amniotic fluid.^[45]

Etiology

Maternal chorioamnionitis occurs when protective mechanisms of the urogenital tract and/or uterus fail during pregnancy or when increased numbers of microbial flora or highly pathogenic microorganisms are introduced into the urogenital environment.^{[45, 46, 47, 48]}

Ascending infection into the vagina, then the cervix, and finally into the uterine cavity, fetal membranes, and placenta is the consequence of many factors (ie, innate host defenses, disrupted healthy bacterial flora, pathologic bacterial load, bacterial virulence factors, and toxin production). A short cervix has been recognized as either a risk factor or a surrogate for microbial invasion of the amniotic fluid.^{[11, 42, 49]}

Urogenital hygiene is obviously important in establishing healthy bacterial flora. Healthy bacteria (ie, lactobacilli)^[50] and natural peptide antibiotics in the vagina and cervix may have roles in preventing infections during pregnancy.^[51] Mucus, phagocytes, and natural antibiotic proteins (ie, lactoferrin, lysozyme, beta defensins) in the cervicovaginal secretions attempt to maintain a normal bacterial flora.^[46] Bacterial interference, mainly produced via lactobacilli living in an acidic vaginal environment and producing bacteriocins, may help to keep pathogenic bacteria from gaining a foothold in the cervicovaginal secretions.^[52]These mechanisms of host protection may be altered in a significant number of pregnant women who develop chorioamnionitis. The use of oral probiotics to alter vaginal flora and potentially reduce morbidities associated with intraamniotic infection has been studied extensively, but no clear cut benefits were realized.^[53]

Oral hygiene may influence rectal and urogenital bacterial flora during pregnancy. Although the theory is controversial, intense interest has focused on a connection among periodontitis, abnormal rectal colonization, and preterm delivery,^{[54, 55]}as well as whether treatment for periodontal disease during pregnancy decrease the incidence of preterm birth.^[56]Orogenital contact may also alter either colonic or urogenital microbial flora and ultimately cause ascending infection and chorioamnionitis, as seen in some case reports.^{[57, 58]}

Currently, researchers are trying to understand how host defense mechanisms prevent urogenital infection during pregnancy. An intense area of research is the concept of bacterial communities living in the cervicovaginal area (microbiome) that are metabolically active to produce biochemicals (metalobome) that support their existence as well as prevent pathogenic bacteria from gaining access to the amniotic cavity and subsequently cause chorioamnionitis.^{[59, 60, 61]}The prevalence and diversity of bacterial species in fetal membranes during preterm labor emphasizes that further research on this topic is needed.^{[62, 63]}Metagenomics uses nonculture, molecular methods to delineate all microbes inhabiting an environment. Thus, the cervicovaginal and intestinal microbiome are under intense scrutiny to understand preterm labor, preterm premature rupture of membranes (PPROM), and chorioamnionitis relative to the mother, and necrotizing enterocolitis, sepsis, and neurologic injury relative to the newborn. Several published reports exist regarding using molecular methods to understand intrauterine infection, fetal inflammation, and preterm delivery.^{[61, 62, 64]}

Clinical events associated with chorioamnionitis include the following:

History of premature birth (with increasing risk at earlier gestational age)
Presence of premature labor
Preterm premature rupture of fetal membranes (before labor onset)
Prolonged rupture of the fetal membranes (>18 hours)

A retrospective study (2012-2015) suggests that prolonged spontaneous active labor beyond the median not only significantly raises the risk of chorioamnionitis but also increases the odds of cesarean delivery.^[65]

In a report of patients with clinical signs and symptoms of chorioamnionitis at term, and using both cultivation and molecular techniques of amniotic fluid, investigators noted almost 40% of women clinically diagnosed with chorioamnionitis did not have any evidence of bacteria in the amniotic cavity.^[66]Additionally, nearly 50% did not have evidence of acute inflammatory lesions of the placenta (ie, histologic chorioamnionitis). Thus, other causes of signs and symptoms that resemble maternal chorioamnionitis must be sought.

Epidural anesthesia during labor is associated with maternal fever^[67]and fetal tachycardia (see Special Concerns in the Diagnostic Considerations section). A sterile inflammatory response in the placenta and the fetus has been shown to be associated with epidural-related maternal fever.^[68]Other conditions, such as dehydration or maternal exhaustion during labor, may result in maternal fever and must also be considered as causes of the febrile state.

United States data

The prevalence of maternal chorioamnionitis in the United States varies with different publications, but it appears to be inversely correlated with gestational age at birth. In a 2014 study that assessed the entire US population and linked infant birth and death certificate files for the year 2008, the prevalence of chorioamnionitis was 9.7 per 1000 live births.^[69]Studies that looked at placentas found histologic chorioamnionitis present in 3%-5% of term placentas and in 94% of placentas delivered at 21-24 weeks of gestation.^[31]

The risk of chorioamnionitis increases based on health conditions and behaviors, as outlined in the Pathophysiology section. Furthermore, factors such as gestational age, economic conditions, and ethnic differences influence the incidence. Histopathology of the placenta suggests inflammation may occur in the normal course of parturition at term gestation, thus complicating the definition of chorioamnionitis. An increase in histopathologic chorioamnionitis is noted in cases of preterm birth as compared with delivery of the healthy term infant. Signs of placental inflammation are present in 42% of extremely low birth weight infants.^[70]Most investigators agree that infection is directly or indirectly associated with 40%-60% of all preterm births.^[71]

Infants exposed to maternal acute chorioamnionitis are at increased risk for early-onset sepsis (EOS). The risk is modified by gestational age and maternal treatment with intrapartum antibiotics. Data from the 1980s and 1990s showed that asymptomatic infants born at term gestation to mothers who received intrapartum treatment for clinical chorioamnionitis have a 1.5% incidence rate of positive blood cultures, whereas symptomatic term infants with chorioamnionitis born to mothers who received intrapartum treatment have a 13% incidence rate of positive cultures 13%.^[72]

More recent reports continue to indicate that the risk of EOS in infants born to women with chorioamnionitis remains strongly dependent on gestational age, but this risk is much lower compared to old data. In three reports including 1892 infants born at 35 weeks or more of gestation to mothers with clinical chorioamnionitis,^{[73, 74, 75]}the rates of EOS (positive blood culture at < 72 hours of age) were only 0.47%, 1.24%, and 0.72% (number needed to treat [NNT] to prevent one infection: 80-210). In contrast, 4.8%-16.9% of preterm infants exposed to chorioamnionitis develop EOS (NNT: 6-21).^{[4, 76]} None of these studies stratified risk according to presence or absence of clinical signs of illness; however, more recent data from the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network suggest the risk to be very low in asymptomatic late preterm and term neonates.^[77]

International data

Developed countries (eg, Canada, Western Europe, Australia) probably have an incidence equal to, or perhaps even less than, the rate of chorioamnionitis observed in the United States. In underdeveloped countries, premature rupture of membranes has a strong association with chorioamnionitis, and chorioamnionitis in this setting results in preterm birth with a high mortality rate.^[78]Classic studies by Naeye et al demonstrated that malnourished pregnant women in Africa had a higher risk of ascending urogenital infection with subsequent amniotic fluid infection.^[79] Infection in these malnourished women in Africa was attributed to a decrease in host defense factors in amniotic fluid that regularly prevents disease in this liquor.^[80]In developed countries where women receive suboptimal care and have poor nutrition during pregnancy, a higher incidence of infection can be expected because of altered immune defenses.^[81]

The bacterial pathogens that cause EOS in developing countries differ from the microbes that cause disease in the United States and other more developed countries, with Klebsiella pneumonia and Pseudomonas aeruginosa being the most common organisms in two reports from India and Pakistan.^{[82, 83]} For ill-defined reasons, the prevalence of group B streptococcal (GBS) disease is lower in developing countries. It is speculated that as developing countries sustain economic development, the prevalence of different bacterial pathogens assumes a profile closer to that of developed countries.

Race-, sex-, and age-related demographics

In select populations, race may increase the risk of maternal chorioamnionitis and preterm delivery.^[84]Studying histologic chorioamnionitis and preterm birth, Holzman et al observed evidence of inflammatory pathology in 12% of placentas from white women and women of other races compared to 55% in black women.^[85] However, it is difficult to separate race form other hostile environmental circumstances (eg, violence, inadequate prenatal care, malnutrition) that could lead to chorioamnionitis and adverse maternal and neonatal outcomes.

Existing data on the role of sex in EOS are conflicting. Although some researchers identified male sex as a risk factor for EOS,^[17]others failed to demonstrate this association.^{[86, 21]}Advanced maternal age alone, defined as being older than 35 years, has not been identified as a risk factor for chorioamnionitis. However, teenage pregnancy raises the risk of chorioamnionitis.^{[87, 88, 89]}

Maternal sequelae

Acute chorioamnionitis may result in labor abnormalities (dysfunctional labor) that increase the risk for cesarean delivery, uterine atony, and postpartum bleeding, as well as the need for blood transfusion.^{[2, 90]}These complications are likely to occur more often when the amniotic fluid is infected with invasive organisms (eg, E coli and group B Streptococcus [GBS]) as compared with low-virulence organisms (eg, Ureaplasma urealyticum).^[91]Chorioamnionitis may also lead to the development of other infectious complications, including endometritis, localized pelvic infections requiring drainage, septic pelvic thrombophlebitis, and intraabdominal infections.^[92]More serious sequelae such as sepsis, coagulopathy, and adult respiratory distress syndrome are rare, especially when treatment with broad-spectrum antibiotics is initiated. Additionally, chorioamnionitis may initiate uteroplacental bleeding or a placental abruption.^[93] The risk of intrauterine infection is increased in placenta previa and may manifest with vaginal bleeding.^[94]

Neonatal sequelae

The most serious risks of neonatal exposure to chorioamnionitis are preterm delivery^[95]and early-onset neonatal infections (especially sepsis and pneumonia). Other adverse outcomes include perinatal death, asphyxia, intraventricular hemorrhage (IVH), cerebral white matter damage, and long-term disability (including cerebral palsy), as well as other morbidities related to preterm birth.^{[96, 97]}The outcome of neonatal infections depends on the causative organism, the nature of the infection, the time of infection onset to time of administration of appropriate therapy, the symptoms at time of birth, and the gestational age of the infant. Prematurity and birth defects are confounding factors that must be considered when a prognosis is offered to parents or caregivers of an infected newborn. Outcomes may not be evident during the neonatal period, and long-term follow-up care is indicated in these infected neonates.

Neonatal mortality and morbidity

In a study that evaluated the whole US population and linked infant birth and death certificate files for the year 2008, the neonatal mortality rate for infants exposed to chorioamnionitis was 1.40 per1000 live births (LB) versus 0.81 per 1000 LB for infants without chorioamnionitis, with an odds ratio (OR) of 1.72 and a 95% confidence interval (CI) 1.20-2.45.^[69]The OR for neonatal death for infants with chorioamnionitis exposure who received antibiotics versus those who did not was 0.69 (95% CI = 0.21-2.26).^[69] In another study of infants born at 23-32 weeks' gestation with evidence of intrauterine infection and inflammation, the neonatal death rate was 9.9%-11.1%.^[98]

Preterm infants born to mothers with chorioamnionitis have unfavorable short-term (meningitis and intraventricular hemorrhage and periventricular leukomalacia) and long-term (cerebral palsy and neurodevelopmental impairment) neurologic outcomes.^{[99, 100]} Cerebral palsy (CP)^[101] and cognitive impairment without CP^[102] have been linked to exposure to maternal chorioamnionitis. In particular, funisitis and the fetal inflammatory response syndrome have been associated with white matter brain injury or periventricular leukomalacia that is linked to activation of cytokine networks.^{[103, 104]} Interleukin (IL)-1beta, IL-6, IL-8, IL-17, IL-18, and tumor necrosis factor (TNF)-alpha are among the cytokines identified as agents related to the fetal inflammatory response syndrome (FIRS) that results in brain injury.^{[105, 106, 107]}However, more recent systematic reviews suggest that the evidence for a causal or associative role of chorioamnionitis in CP is weak^[108]and that improvements in neonatal intensive care may have attenuated the impact of chorioamnionitis on brain health outcomes.^[109]

The relationship of chorioamnionitis and neonatal cardiopulmonary morbidity is conflicting. Different studies have evaluated the risk of respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), and childhood asthma after fetal exposure to chorioamnionitis. Although some studies showed chorioamnionitis to be associated with lower risk of RDS,^{[110, 111]}other studies found an increased risk of RDS^{[111, 112]}or no association after adjusting to other variables.^[99] Similar conflicting data exist for the link of chorioamnionitis and BPD; however, a 2017 French national prospective, population-based, cohort study that included 2513 live-born singletons delivered at 24-31 weeks of gestation and 1731 placentas concluded that histologic chorioamnionitis is not associated with BPD.^[113]

Chorioamnionitis caused by Ureaplasma has been studied extensively^[114](including in animal models) and has been linked to congenital pneumonia, prolonged mechanical ventilation, and cytokine release in the neonatal lungs with subsequent development of BPD.^[115]However, studies that looked at antibiotic therapy with erythromycin to reduce the incidence BPD when the neonatal lungs are colonized or infected with Ureaplasma have been disappointing. More recent studies with azithromycin are encouraging.^{[116, 117]}

The link between fetal exposure to chorioamnionitis and the future development of childhood asthma was implied by a systematic review but there was much variation in the included studies with regard to the type of maternal infection, age of the children, and methods of exposure ascertainment that made the conclusion less certain.^[118]Lastly, with regard to the association between chorioamnionitis and patent ductus arteriosus, two meta-analyses reached opposing conclusions about the association.^{[119, 120]}

Patient Education

Parents or other caregivers of infected neonates need specific instructions about the subsequent care of these infants. This is particularly true for secondary complications associated with such infections. For example, parents/caregivers of an infant with meningitis that has postinfectious hydrocephalus requiring ventriculoperitoneal shunt placement need to have specific instructions about shunt-related malfunction or shunt-related infection. Education of the parents/caregivers related to the recognition and management of seizures should be mandatory before discharge.

Similarly, parents/caregivers of patients with long-term pulmonary complications of congenital pneumonia may require specific education (eg, administration of oxygen or use of bronchodilators at home). Parental education in neonatal resuscitation is indicated for many graduates of the neonatal intensive care unit (NICU).

Clinical Presentation

Snyder M, Crawford P, Jamieson B, Neher JO. Clinical inquiries. What treatment approach to intrapartum maternal fever has the best fetal outcomes?. J Fam Pract. 2007 May. 56(5):401-2. [Medline].
Higgins RD, Saade G, Polin RA, et al, for the Chorioamnionitis Workshop Participants. Evaluation and management of women and newborns with a maternal diagnosis of chorioamnionitis: summary of a workshop. Obstet Gynecol. 2016 Mar. 127(3):426-36. [Medline].
Barth WH Jr. Lost in translation: the changing language of our specialty. Obstet Gynecol. 2016 Mar. 127(3):423-5. [Medline].
Benitz WE, Wynn JL, Polin RA. Reappraisal of guidelines for management of neonates with suspected early-onset sepsis. J Pediatr. 2015 Apr. 166(4):1070-4. [Medline].
Horvath B, Lakatos F, Toth C, Bodecs T, Bodis J. Silent chorioamnionitis and associated pregnancy outcomes: a review of clinical data gathered over a 16-year period. J Perinat Med. 2014 Jul. 42(4):441-7. [Medline].
Apantaku O, Mulik V. Maternal intra-partum fever. J Obstet Gynaecol. 2007 Jan. 27(1):12-5. [Medline].
Hsu CD, Meaddough E, Hong SF, Aversa K, Lu LC, Copel JA. Elevated amniotic fluid nitric oxide metabolites and interleukin-6 in intra-amniotic infection. J Soc Gynecol Investig. 1998 Jan-Feb. 5(1):21-4. [Medline].
Buhimschi CS, Bhandari V, Hamar BD, et al. Proteomic profiling of the amniotic fluid to detect inflammation, infection, and neonatal sepsis. PLoS Med. 2007 Jan. 4(1):e18. [Medline].
Joram N, Boscher C, Denizot S. Umbilical cord blood procalcitonin and C reactive protein concentrations as markers for early diagnosis of very early onset neonatal infection. Arch Dis Child Fetal Neonatal Ed. 2006 Jan. 91(1):F65-6. [Medline].
Hedegaard SS, Wisborg K, Hvas AM. Diagnostic utility of biomarkers for neonatal sepsis--a systematic review. Infect Dis (Lond). 2015 Mar. 47(3):117-24. [Medline].
Hassan S, Romero R, Hendler I, et al. A sonographic short cervix as the only clinical manifestation of intra-amniotic infection. J Perinat Med. 2006. 34(1):13-9. [Medline].
Kusanovic JP, Espinoza J, Romero R, et al. Clinical significance of the presence of amniotic fluid 'sludge' in asymptomatic patients at high risk for spontaneous preterm delivery. Ultrasound Obstet Gynecol. 2007 Oct. 30(5):706-14. [Medline].
Rizzo G, Capponi A, Vlachopoulou A, Angelini E, Grassi C, Romanini C. Ultrasonographic assessment of the uterine cervix and interleukin-8 concentrations in cervical secretions predict intrauterine infection in patients with preterm labor and intact membranes. Ultrasound Obstet Gynecol. 1998 Aug. 12(2):86-92. [Medline].
Reilly SD, Faye-Petersen OM. Chorioamnionitis and funisitis. NeoReviews. Sept 2008. 9(9):e411-7. [Full Text].
Escobar GJ. The neonatal "sepsis work-up": personal reflections on the development of an evidence-based approach toward newborn infections in a managed care organization. Pediatrics. 1999 Jan. 103(1 suppl E):360-73. [Medline].
Callaghan WM, MacDorman MF, Rasmussen SA, Qin C, Lackritz EM. The contribution of preterm birth to infant mortality rates in the United States. Pediatrics. 2006 Oct. 118(4):1566-73. [Medline].
Dutta S, Reddy R, Sheikh S, Kalra J, Ray P, Narang A. Intrapartum antibiotics and risk factors for early onset sepsis. Arch Dis Child Fetal Neonatal Ed. 2010 Mar. 95(2):F99-103. [Medline].
Larsen JW, Sever JL. Group B Streptococcus and pregnancy: a review. Am J Obstet Gynecol. 2008 Apr. 198(4):440-8; discussion 448-50. [Medline].
Schrag SJ, Verani JR. Intrapartum antibiotic prophylaxis for the prevention of perinatal group B streptococcal disease: experience in the United States and implications for a potential group B streptococcal vaccine. Vaccine. 2013 Aug 28. 31 suppl 4:D20-6. [Medline].
Stoll BJ, Hansen NI, Sanchez PJ, et al, for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Early onset neonatal sepsis: the burden of group B streptococcal and E. coli disease continues. Pediatrics. 2011 May. 127(5):817-26. [Medline].
Bizzarro MJ, Dembry LM, Baltimore RS, Gallagher PG. Changing patterns in neonatal Escherichia coli sepsis and ampicillin resistance in the era of intrapartum antibiotic prophylaxis. Pediatrics. 2008 Apr. 121(4):689-96. [Medline].
Bratu S, Eramo A, Kopec R. Community-associated methicillin-resistant Staphylococcus aureus in hospital nursery and maternity units. Emerg Infect Dis. 2005 Jun. 11(6):808-13. [Medline].
Andrews WW, Schelonka R, Waites K, Stamm A, Cliver SP, Moser S. Genital tract methicillin-resistant Staphylococcus aureus: risk of vertical transmission in pregnant women. Obstet Gynecol. 2008 Jan. 111(1):113-8. [Medline].
Mazaki-Tovi S, Vaisbuch E. Clinical chorioamnionitis--an ongoing obstetrical conundrum. J Perinat Med. 2016 Jan. 44(1):1-4. [Medline].
Romero R, Chaemsaithong P, Korzeniewski SJ, et al. Clinical chorioamnionitis at term II: the intra-amniotic inflammatory response. J Perinat Med. 2016 Jan. 44(1):5-22. [Medline].
Romero R, Chaemsaithong P, Korzeniewski SJ, et al. Clinical chorioamnionitis at term III: how well do clinical criteria perform in the identification of proven intra-amniotic infection?. J Perinat Med. 2016 Jan. 44(1):23-32. [Medline].
Romero R, Chaemsaithong P, Docheva N, et al. Clinical chorioamnionitis at term IV: the maternal plasma cytokine profile. J Perinat Med. 2016 Jan. 44(1):77-98. [Medline].
Romero R, Chaemsaithong P, Docheva N, et al. Clinical chorioamnionitis at term V: umbilical cord plasma cytokine profile in the context of a systemic maternal inflammatory response. J Perinat Med. 2016 Jan. 44(1):53-76. [Medline].
Romero R, Chaemsaithong P, Docheva N, et al. Clinical chorioamnionitis at term VI: acute chorioamnionitis and funisitis according to the presence or absence of microorganisms and inflammation in the amniotic cavity. J Perinat Med. 2016 Jan. 44(1):33-51. [Medline].
Committee on Obstetric Practice. Committee opinion no. 712: Intrapartum management of intraamniotic infection. Obstet Gynecol. 2017 Aug. 130(2):e95-e101. [Medline].
Kim CJ, Romero R, Chaemsaithong P, Chaiyasit N, Yoon BH, Kim YM. Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance. Am J Obstet Gynecol. 2015 Oct. 213 (4 suppl):S29-52. [Medline].
Hitti J, Hillier SL, Agnew KJ, Krohn MA, Reisner DP, Eschenbach DA. Vaginal indicators of amniotic fluid infection in preterm labor. Obstet Gynecol. 2001 Feb. 97(2):211-9. [Medline].
Donders GG, Van Calsteren K, Bellen G, et al. Predictive value for preterm birth of abnormal vaginal flora, bacterial vaginosis and aerobic vaginitis during the first trimester of pregnancy. BJOG. 2009 Sep. 116(10):1315-24. [Medline].
Al-Adnani M, Sebire NJ. The role of perinatal pathological examination in subclinical infection in obstetrics. Best Pract Res Clin Obstet Gynaecol. 2007 Jun. 21(3):505-21. [Medline].
Sheiner E, Mazor-Drey E, Levy A. Asymptomatic bacteriuria during pregnancy. J Matern Fetal Neonatal Med. 2009 May. 22(5):423-7. [Medline].
Anderson BL, Simhan HN, Simons KM, Wiesenfeld HC. Untreated asymptomatic group B streptococcal bacteriuria early in pregnancy and chorioamnionitis at delivery. Am J Obstet Gynecol. 2007 Jun. 196(6):524.e1-5. [Medline].
Sangkomkamhang US, Lumbiganon P, Prasertcharoensuk W, Laopaiboon M. Antenatal lower genital tract infection screening and treatment programs for preventing preterm delivery. Cochrane Database Syst Rev. 2015 Feb 1. CD006178. [Medline].
Siqueira FM, Cota LO, Costa JE, Haddad JP, Lana AM, Costa FO. Intrauterine growth restriction, low birth weight, and preterm birth: adverse pregnancy outcomes and their association with maternal periodontitis. J Periodontol. 2007 Dec. 78(12):2266-76. [Medline].
Aly H, Alhabashi G, Hammad TA, Owusu-Ansah S, Bathgate S, Mohamed M. ABO phenotype and other risk factors associated with chorioamnionitis. J Pediatr. 2008 Jul. 153(1):16-8. [Medline].
Hadley EE, Discacciati A, Costantine MM,. Maternal obesity is associated with chorioamnionitis and earlier indicated preterm delivery among expectantly managed women with preterm premature rupture of membranes. J Matern Fetal Neonatal Med. 2017 Sep 22. 1-8. [Medline].
Lee SE, Romero R, Park CW, Jun JK, Yoon BH. The frequency and significance of intraamniotic inflammation in patients with cervical insufficiency. Am J Obstet Gynecol. 2008 Jun. 198(6):633.e1-8. [Medline].
Vaisbuch E, Hassan SS, Mazaki-Tovi S, et al. Patients with an asymptomatic short cervix (<or=15 mm) have a high rate of subclinical intraamniotic inflammation: implications for patient counseling. Am J Obstet Gynecol. 2010 May. 202(5):433.e1-8. [Medline].
Heinemann J, Gillen G, Sanchez-Ramos L, Kaunitz AM. Do mechanical methods of cervical ripening increase infectious morbidity? A systematic review. Am J Obstet Gynecol. 2008 Aug. 199(2):177-87; discussion 187-8. [Medline].
Alfirevic Z, Kelly AJ, Dowswell T. Intravenous oxytocin alone for cervical ripening and induction of labour. Cochrane Database Syst Rev. 2009 Oct 7. CD003246. [Medline].
King AE, Kelly RW, Sallenave JM, Bocking AD, Challis JR. Innate immune defences in the human uterus during pregnancy. Placenta. 2007 Nov-Dec. 28(11-12):1099-106. [Medline].
Hein M, Valore EV, Helmig RB. Antimicrobial factors in the cervical mucus plug. Am J Obstet Gynecol. 2002 Jul. 187(1):137-44. [Medline].
Akinbi HT, Narendran V, Pass AK. Host defense proteins in vernix caseosa and amniotic fluid. Am J Obstet Gynecol. 2004 Dec. 191(6):2090-6. [Medline].
Soto E, Espinoza J, Nien JK, et al. Human beta-defensin-2: a natural antimicrobial peptide present in amniotic fluid participates in the host response to microbial invasion of the amniotic cavity. J Matern Fetal Neonatal Med. 2007 Jan. 20(1):15-22. [Medline].
Gomez R, Romero R, Nien JK. A short cervix in women with preterm labor and intact membranes: a risk factor for microbial invasion of the amniotic cavity. Am J Obstet Gynecol. 2005 Mar. 192(3):678-89. [Medline].
Wilks M, Wiggins R, Whiley A. Identification and H(2)O(2) production of vaginal lactobacilli from pregnant women at high risk of preterm birth and relation with outcome. J Clin Microbiol. 2004 Feb. 42(2):713-7. [Medline].
Balu RB, Savitz DA, Ananth CV. Bacterial vaginosis, vaginal fluid neutrophil defensins, and preterm birth. Obstet Gynecol. 2003 May. 101(5 Pt 1):862-8. [Medline].
Simoes JA, Aroutcheva A, Heimler I. Bacteriocin susceptibility of Gardnerella vaginalis and its relationship to biotype, genotype, and metronidazole susceptibility. Am J Obstet Gynecol. 2001 Nov. 185(5):1186-90. [Medline].
Griffin C. Probiotics in obstetrics and gynaecology. Aust N Z J Obstet Gynaecol. 2015 Jun. 55(3):201-9. [Medline].
McGaw T. Periodontal disease and preterm delivery of low-birth-weight infants. J Can Dent Assoc. 2002 Mar. 68(3):165-9. [Medline].
Urban E, Radnai M, Novak T. Distribution of anaerobic bacteria among pregnant periodontitis patients who experience preterm delivery. Anaerobe. 2006 Feb. 12(1):52-7. [Medline].
Polyzos NP, Polyzos IP, Mauri D, et al. Effect of periodontal disease treatment during pregnancy on preterm birth incidence: a metaanalysis of randomized trials. Am J Obstet Gynecol. 2009 Mar. 200(3):225-32. [Medline].
Dixon NG, Ebright D, Defrancesco MA. Orogenital contact: a cause of chorioamnionitis?. Obstet Gynecol. 1994 Oct. 84(4 Pt 2):654-5. [Medline].
Hansen LM, Dorsey TA, Batzer FA. Capnocytophaga chorioamnionitis after oral sex. Obstet Gynecol. 1996 Oct. 88(4 Pt 2):731. [Medline].
Freitas AC, Chaban B, Bocking A, et al, for the VOGUE Research Group. The vaginal microbiome of pregnant women is less rich and diverse, with lower prevalence of Mollicutes, compared to non-pregnant women. Sci Rep. 2017 Aug 23. 7(1):9212. [Medline].
Parnell LA, Briggs CM, Mysorekar IU. Maternal microbiomes in preterm birth: Recent progress and analytical pipelines. Semin Perinatol. 2017 Nov. 41(7):392-400. [Medline].
Stout MJ, Zhou Y, Wylie KM, Tarr PI, Macones GA, Tuuli MG. Early pregnancy vaginal microbiome trends and preterm birth. Am J Obstet Gynecol. 2017 Sep. 217(3):356.e1-356.e18. [Medline].
Doyle RM, Harris K, Kamiza S, et al. Bacterial communities found in placental tissues are associated with severe chorioamnionitis and adverse birth outcomes. PLoS One. 2017. 12(7):e0180167. [Medline].
Pelzer E, Gomez-Arango LF, Barrett HL, Nitert MD. Review: Maternal health and the placental microbiome. Placenta. 2017 Jun. 54:30-7. [Medline].
Stafford GP, Parker JL, Amabebe E, et al. Spontaneous preterm birth is associated with differential expression of vaginal metabolites by lactobacilli-dominated microflora. Front Physiol. 2017. 8:615. [Medline].
Hoppe KK, Schiff MA, Benedetti TJ, Delaney S. Duration of spontaneous active labor and perinatal outcomes using contemporary labor curves. Am J Perinatol. 2018 Apr 25. 111(6):1467-75. [Medline].
Romero R, Miranda J, Kusanovic JP, e al. Clinical chorioamnionitis at term I: microbiology of the amniotic cavity using cultivation and molecular techniques. J Perinat Med. 2015 Jan. 43(1):19-36. [Medline].
Segal S. Labor epidural analgesia and maternal fever. Anesth Analg. 2010 Dec. 111(6):1467-75. [Medline].
Sultan P, David AL, Fernando R, Ackland GL. Inflammation and epidural-related maternal fever: proposed mechanisms. Anesth Analg. 2016 May. 122(5):1546-53. [Medline].
Malloy MH. Chorioamnionitis: epidemiology of newborn management and outcome United States 2008. J Perinatol. 2014 Aug. 34(8):611-5. [Medline].
Verma RP, Kaplan C, Southerton K, Niwas R, Verma R, Fang H. Placental histopathology in the extremely low birth weight infants. Fetal Pediatr Pathol. 2008 Aug. 27(2):53-61. [Medline].
Newton ER. Preterm labor, preterm premature rupture of membranes, and chorioamnionitis. Clin Perinatol. 2005 Sep. 32(3):571-600. [Medline].
Mecredy RL, Wiswell TE, Hume RF. Outcome of term gestation neonates whose mothers received intrapartum antibiotics for suspected chorioamnionitis. Am J Perinatol. 1993 Sep. 10(5):365-8. [Medline].
Jackson GL, Engle WD, Sendelbach DM, et al. Are complete blood cell counts useful in the evaluation of asymptomatic neonates exposed to suspected chorioamnionitis?. Pediatrics. 2004 May. 113(5):1173-80. [Medline].
Jackson GL, Rawiki P, Sendelbach D, Manning MD, Engle WD. Hospital course and short-term outcomes of term and late preterm neonates following exposure to prolonged rupture of membranes and/or chorioamnionitis. Pediatr Infect Dis J. 2012 Jan. 31(1):89-90. [Medline].
Kiser C, Nawab U, McKenna K, Aghai ZH. Role of guidelines on length of therapy in chorioamnionitis and neonatal sepsis. Pediatrics. 2014 Jun. 133(6):992-8. [Medline].
Gagliardi L, Rusconi F, Bellu R, Zanini R, Italian Neonatal Network. Association of maternal hypertension and chorioamnionitis with preterm outcomes. Pediatrics. 2014 Jul. 134(1):e154-61. [Medline].
Wortham JM, Hansen NI, Schrag SJ, et al, for the Eunice Kennedy Shriver NICHD Neonatal Research Network. Chorioamnionitis and culture-confirmed, early-onset neonatal infections. Pediatrics. 2016 Jan. 137 (1):[Medline].
Obi SN, Ozumba BC. Pre-term premature rupture of fetal membranes: the dilemma of management in a developing nation. J Obstet Gynaecol. 2007 Jan. 27(1):37-40. [Medline].
Naeye RL, Tafari N, Judge D, Gilmour D, Marboe C. Amniotic fluid infections in an African city. J Pediatr. 1977 Jun. 90(6):965-70. [Medline].
Appelbaum PC, Ross SM, Dhupelia I, Naeye RL. The effect of diet supplementation and addition of zinc in vitro on the growth-supporting property of amniotic fluid in African women. Am J Obstet Gynecol. 1979 Sep 1. 135(1):82-4. [Medline].
Katona P, Katona-Apte J. The interaction between nutrition and infection. Clin Infect Dis. 2008 May 15. 46(10):1582-8. [Medline].
Chacko B, Sohi I. Early onset neonatal sepsis. Indian J Pediatr. 2005 Jan. 72(1):23-6. [Medline].
Alam MM, Saleem AF, Shaikh AS, Munir O, Qadir M. Neonatal sepsis following prolonged rupture of membranes in a tertiary care hospital in Karachi, Pakistan. J Infect Dev Ctries. 2014 Jan 15. 8(1):67-73. [Medline].
Fassett MJ, Wing DA, Getahun D. Temporal trends in chorioamnionitis by maternal race/ethnicity and gestational age (1995-2010). Int J Reprod Med. 2013. 2013:906467. [Medline].
Holzman C, Lin X, Senagore P, Chung H. Histologic chorioamnionitis and preterm delivery. Am J Epidemiol. 2007 Oct 1. 166(7):786-94. [Medline].
Tsai CH, Chen YY, Wang KG, Chen CY, Chen CP. Characteristics of early-onset neonatal sepsis caused by Escherichia coli. Taiwan J Obstet Gynecol. 2012 Mar. 51(1):26-30. [Medline].
Jolly MC, Sebire N, Harris J, Robinson S, Regan L. Obstetric risks of pregnancy in women less than 18 years old. Obstet Gynecol. 2000 Dec. 96(6):962-6. [Medline].
Raatikainen K, Heiskanen N, Verkasalo PK, Heinonen S. Good outcome of teenage pregnancies in high-quality maternity care. Eur J Public Health. 2006 Apr. 16(2):157-61. [Medline].
Kawakita T, Wilson K, Grantz KL, Landy HJ, Huang CC, Gomez-Lobo V. Adverse maternal and neonatal outcomes in adolescent pregnancy. J Pediatr Adolesc Gynecol. 2016 Apr. 29(2):130-6. [Medline].
Mark SP, Croughan-Minihane MS, Kilpatrick SJ. Chorioamnionitis and uterine function. Obstet Gynecol. 2000 Jun. 95(6 Pt 1):909-12. [Medline].
Silver RK, Gibbs RS, Castillo M. Effect of amniotic fluid bacteria on the course of labor in nulliparous women at term. Obstet Gynecol. 1986 Nov. 68(5):587-92. [Medline].
Rouse DJ, Landon M, Leveno KJ, et al, for the National Institute of Child Health And Human Development, Maternal-Fetal Medicine Units Network. The Maternal-Fetal Medicine Units cesarean registry: chorioamnionitis at term and its duration-relationship to outcomes. Am J Obstet Gynecol. 2004 Jul. 191(1):211-6. [Medline].
Nath CA, Ananth CV, Smulian JC, Shen-Schwarz S, Kaminsky L. Histologic evidence of inflammation and risk of placental abruption. Am J Obstet Gynecol. 2007 Sep. 197(3):319.e1-6. [Medline].
Madan I, Romero R, Kusanovic JP, et al. The frequency and clinical significance of intra-amniotic infection and/or inflammation in women with placenta previa and vaginal bleeding: an unexpected observation. J Perinat Med. 2010 May. 38(3):275-9. [Medline].
Bastek JA, Weber AL, McShea MA, Ryan ME, Elovitz MA. Prenatal inflammation is associated with adverse neonatal outcomes. Am J Obstet Gynecol. 2014 May. 210(5):450.e1-10. [Medline].
Ericson JE, Laughon MM. Chorioamnionitis: implications for the neonate. Clin Perinatol. 2015 Mar. 42(1):155-65, ix. [Medline].
Pugni L, Pietrasanta C, Acaia B, et al. Chorioamnionitis and neonatal outcome in preterm infants: a clinical overview. J Matern Fetal Neonatal Med. 2016. 29(9):1525-9. [Medline].
Goldenberg RL, Andrews WW, Faye-Petersen OM, Cliver SP, Goepfert AR, Hauth JC. The Alabama preterm birth study: corticosteroids and neonatal outcomes in 23- to 32-week newborns with various markers of intrauterine infection. Am J Obstet Gynecol. 2006 Oct. 195(4):1020-4. [Medline].
Soraisham AS, Singhal N, McMillan DD, Sauve RS, Lee SK. A multicenter study on the clinical outcome of chorioamnionitis in preterm infants. Am J Obstet Gynecol. 2009 Apr. 200(4):372.e1-6. [Medline].
Andrews WW, Goldenberg RL, Faye-Petersen O, Cliver S, Goepfert AR, Hauth JC. The Alabama Preterm Birth study: polymorphonuclear and mononuclear cell placental infiltrations, other markers of inflammation, and outcomes in 23- to 32-week preterm newborn infants. Am J Obstet Gynecol. 2006 Sep. 195(3):803-8. [Medline].
Neufeld MD, Frigon C, Graham AS, Mueller BA. Maternal infection and risk of cerebral palsy in term and preterm infants. J Perinatol. 2005 Feb. 25(2):108-13. [Medline].
Versland LB, Sommerfelt K, Elgen I. Maternal signs of chorioamnionitis: persistent cognitive impairment in low-birthweight children. Acta Paediatr. 2006 Feb. 95(2):231-5. [Medline].
Bashiri A, Burstein E, Mazor M. Cerebral palsy and fetal inflammatory response syndrome: a review. J Perinat Med. 2006. 34(1):5-12. [Medline].
Lu HY, Zhang Q, Wang QX, Lu JY. Contribution of histologic chorioamnionitis and fetal inflammatory response syndrome to increased risk of brain injury in infants with preterm premature rupture of membranes. Pediatr Neurol. 2016 Aug. 61:94-98.e1. [Medline].
Hagberg H, Mallard C, Jacobsson B. Role of cytokines in preterm labour and brain injury. BJOG. 2005 Mar. 112 Suppl 1:16-8. [Medline].
Kallapur SG, Presicce P, Rueda CM, Jobe AH, Chougnet CA. Fetal immune response to chorioamnionitis. Semin Reprod Med. 2014 Jan. 32(1):56-67. [Medline].
O'Shea TM, Shah B, Allred EN, et al, for the ELGAN Study Investigators. Inflammation-initiating illnesses, inflammation-related proteins, and cognitive impairment in extremely preterm infants. Brain Behav Immun. 2013 Mar. 29:104-12. [Medline].
Shi Z, Ma L, Luo K, et al. Chorioamnionitis in the development of cerebral palsy: a meta-analysis and systematic review. Pediatrics. 2017 Jun. 139(6):[Medline].
Chau V, McFadden DE, Poskitt KJ, Miller SP. Chorioamnionitis in the pathogenesis of brain injury in preterm infants. Clin Perinatol. 2014 Mar. 41(1):83-103. [Medline].
Liu Z, Tang Z, Li J, Yang Y. Effects of placental inflammation on neonatal outcome in preterm infants. Pediatr Neonatol. 2014 Feb. 55(1):35-40. [Medline].
Been JV, Rours IG, Kornelisse RF, et al. Histologic chorioamnionitis, fetal involvement, and antenatal steroids: effects on neonatal outcome in preterm infants. Am J Obstet Gynecol. 2009 Dec. 201(6):587.e1-8. [Medline].
Jones MH, Corso AL, Tepper RS, et al. Chorioamnionitis and subsequent lung function in preterm infants. PLoS One. 2013. 8(12):e81193. [Medline].
Torchin H, Lorthe E, Goffinet F, et al. Histologic chorioamnionitis and bronchopulmonary dysplasia in preterm infants: the epidemiologic study on low gestational ages 2 cohort. J Pediatr. 2017 Aug. 187:98-104.e3. [Medline].
Kallapur SG, Kramer BW, Jobe AH. Ureaplasma and BPD. Semin Perinatol. 2013 Apr. 37(2):94-101. [Medline].
Viscardi RM, Kallapur SG. Role of ureaplasma respiratory tract colonization in bronchopulmonary dysplasia pathogenesis: current concepts and update. Clin Perinatol. 2015 Dec. 42(4):719-38. [Medline].
Nair V, Loganathan P, Soraisham AS. Azithromycin and other macrolides for prevention of bronchopulmonary dysplasia: a systematic review and meta-analysis. Neonatology. 2014. 106(4):337-47. [Medline].
Smith C, Egunsola O, Choonara I, Kotecha S, Jacqz-Aigrain E, Sammons H. Use and safety of azithromycin in neonates: a systematic review. BMJ Open. 2015 Dec 9. 5(12):e008194. [Medline].
Zhu T, Zhang L, Qu Y, Mu D. Meta-analysis of antenatal infection and risk of asthma and eczema. Medicine (Baltimore). 2016 Aug. 95(35):e4671. [Medline].
Behbodi E, Villamor-Martinez E, Degraeuwe PL, Villamor E. Chorioamnionitis appears not to be a risk factor for patent ductus arteriosus in preterm infants: a systematic review and meta-analysis. Sci Rep. 2016 Nov 28. 6:37967. [Medline].
Park HW, Choi YS, Kim KS, Kim SN. Chorioamnionitis and patent ductus arteriosus: a systematic review and meta-analysis. PLoS One. 2015. 10(9):e0138114. [Medline].
Mukhopadhyay S, Taylor JA, Von Kohorn I, et al. Variation in sepsis evaluation across a national network of nurseries. Pediatrics. 2017 Mar. 139(3):[Medline].
Pontrelli G, De Crescenzo F, Buzzetti R, et al. Accuracy of serum procalcitonin for the diagnosis of sepsis in neonates and children with systemic inflammatory syndrome: a meta-analysis. BMC Infect Dis. 2017 Apr 24. 17(1):302. [Medline].
Machado JR, Soave DF, da Silva MV, et al. Neonatal sepsis and inflammatory mediators. Mediators Inflamm. 2014. 2014:269681. [Medline].
Aydin M, Barut S, Akbulut HH, Ucar S, Orman A. Application of flow cytometry in the early diagnosis of neonatal sepsis. Ann Clin Lab Sci. 2017 Mar. 47(2):184-90. [Medline].
Ozdemir AA, Elgormus Y. Diagnostic value of presepsin in detection of early-onset neonatal sepsis. Am J Perinatol. 2017 May. 34(6):550-6. [Medline].
Ganesan P, Shanmugam P, Sattar SB, Shankar SL. Evaluation of IL-6, CRP and hs-CRP as early markers of neonatal sepsis. J Clin Diagn Res. 2016 May. 10(5):DC13-7. [Medline].
Yoneda N, Yoneda S, Niimi H, et al. Sludge reflects intra-amniotic inflammation with or without microorganisms. Am J Reprod Immunol. 2018 Feb. 79 (2):2681-4. [Medline].
Adanir I, Ozyuncu O, Gokmen Karasu AF, Onderoglu LS. Amniotic fluid "sludge"; prevalence and clinical significance of it in asymptomatic patients at high risk for spontaneous preterm delivery. J Matern Fetal Neonatal Med. 2018 Jan. 31 (2):135-40. [Medline].
Romem Y, Artal R. C-reactive protein as a predictor for chorioamnionitis in cases of premature rupture of the membranes. Am J Obstet Gynecol. 1984 Nov 1. 150(5 Pt 1):546-50. [Medline].
Sanghvi KP, Tudehope DI. Neonatal bacterial sepsis in a neonatal intensive care unit: a 5 year analysis. J Paediatr Child Health. 1996 Aug. 32(4):333-8. [Medline].
Anim-Somuah M, Smyth RM, Jones L. Epidural versus non-epidural or no analgesia in labour. Cochrane Database Syst Rev. 2011 Dec 7. CD000331. [Medline].
Lieberman E, Lang J, Richardson DK. Intrapartum maternal fever and neonatal outcome. Pediatrics. 2000 Jan. 105(1 Pt 1):8-13. [Medline].
Goetzl L, Evans T, Rivers J. Elevated maternal and fetal serum interleukin-6 levels are associated with epidural fever. Am J Obstet Gynecol. 2002 Oct. 187(4):834-8. [Medline].
Le Ray C, Audibert F, Goffinet F, Fraser W. When to stop pushing: effects of duration of second-stage expulsion efforts on maternal and neonatal outcomes in nulliparous women with epidural analgesia. Am J Obstet Gynecol. 2009 Oct. 201(4):361.e1-7. [Medline].
Heesen M, Klohr S, Rossaint R, Straube S, Van de Velde M. Labour epidural analgesia and anti-infectious management of the neonate: a meta-analysis. J Perinat Med. 2012 Nov. 40(6):625-30. [Medline].
Combs CA, Garite TJ, Lapidus JA, et al, for the Obstetrix Collaborative Research Network. Detection of microbial invasion of the amniotic cavity by analysis of cervicovaginal proteins in women with preterm labor and intact membranes. Am J Obstet Gynecol. 2015 Apr. 212(4):482.e1-12. [Medline].
Vandenbroucke L, Doyen M, Le Lous M, et al. Chorioamnionitis following preterm premature rupture of membranes and fetal heart rate variability. PLoS One. 2017. 12(9):e0184924. [Medline].
Miller JM Jr, Kho MS, Brown HL, Gabert HA. Clinical chorioamnionitis is not predicted by an ultrasonic biophysical profile in patients with premature rupture of membranes. Obstet Gynecol. 1990 Dec. 76(6):1051-4. [Medline].
Vintzileos AM, Campbell WA, Nochimson DJ. Fetal breathing as a predictor of infection in premature rupture of the membranes. Obstet Gynecol. 1986 Jun. 67(6):813-7. [Medline].
Vintzileos AM, Campbell WA, Nochimson DJ. The fetal biophysical profile in patients with premature rupture of the membranes--an early predictor of fetal infection. Am J Obstet Gynecol. 1985 Jul 1. 152(5):510-6. [Medline].
Taketomo CK, Hodding JH, Kraus DM, eds. Lexicomp Pediatric & Neonatal Dosage Handbook with International Trade Names Index. 24th ed. Wolters Kluwer; 2017.
Weinstein L. A multifacited approach to improve patient safety, prevent medical errors and resolve the professional liability crisis. Am J Obstet Gynecol. 2006 Apr. 194(4):1160-5; discussion 1165-7. [Medline].
Donn SM. Medical liability, risk management, and the quality of health care. Semin Fetal Neonatal Med. 2005 Feb. 10(1):3-9. [Medline].
Shwayder JM. Liability in high-risk obstetrics. Obstet Gynecol Clin North Am. 2007 Sep. 34(3):617-25, xiv. [Medline].
Bonadio WA. Medical-legal considerations related to symptom duration and patient outcome after bacterial meningitis. Am J Emerg Med. 1997 Jul. 15(4):420-3. [Medline].
Wu YW, Escobar GJ, Grether JK, Croen LA, Greene JD, Newman TB. Chorioamnionitis and cerebral palsy in term and near-term infants. JAMA. 2003 Nov 26. 290(20):2677-84. [Medline].
Shalak LF, Laptook AR, Jafri HS. Clinical chorioamnionitis, elevated cytokines, and brain injury in term infants. Pediatrics. 2002 Oct. 110(4):673-80. [Medline].
Grether JK, Nelson KB, Walsh E. Intrauterine exposure to infection and risk of cerebral palsy in very preterm infants. Arch Pediatr Adolesc Med. 2003 Jan. 157(1):26-32. [Medline].
Graham EM, Holcroft CJ, Rai KK. Neonatal cerebral white matter injury in preterm infants is associated with culture positive infections and only rarely with metabolic acidosis. Am J Obstet Gynecol. 2004 Oct. 191(4):1305-10. [Medline].
Seubert DE, Huang WM, Wasserman-Hoff R. Medical legal issues in the prevention of prematurity. Clin Perinatol. 2007 Jun. 34(2):309-18, vii. [Medline].
Leighton BL, Halpern SH. Epidural analgesia: effects on labor progress and maternal and neonatal outcome. Semin Perinatol. 2002 Apr. 26(2):122-35. [Medline].
Yancey MK, Zhang J, Schwarz J, Dietrich CS 3rd, Klebanoff M. Labor epidural analgesia and intrapartum maternal hyperthermia. Obstet Gynecol. 2001 Nov. 98(5 Pt 1):763-70. [Medline].
Mantha VR, Vallejo MC, Ramesh V, Phelps AL, Ramanathan S. The incidence of maternal fever during labor is less with intermittent than with continuous epidural analgesia: a randomized controlled trial. Int J Obstet Anesth. 2008 Apr. 17(2):123-9. [Medline].
Riley LE, Celi AC, Onderdonk AB, Roberts DJ, Johnson LC, Tsen LC, et al. Association of epidural-related fever and noninfectious inflammation in term labor. Obstet Gynecol. 2011 Mar. 117(3):588-95. [Medline].
Lieberman E, Lang JM, Frigoletto F Jr. Epidural analgesia, intrapartum fever, and neonatal sepsis evaluation. Pediatrics. 1997 Mar. 99(3):415-9. [Medline].
Goldenberg RL, Andrews WW, Goepfert AR, et al. The Alabama Preterm Birth Study: umbilical cord blood Ureaplasma urealyticum and Mycoplasma hominis cultures in very preterm newborn infants. Am J Obstet Gynecol. 2008 Jan. 198(1):43.e1-5. [Medline].
Payne MS, Goss KC, Connett GJ, et al. Molecular microbiological characterization of preterm neonates at risk of bronchopulmonary dysplasia. Pediatr Res. 2010 Apr. 67(4):412-8. [Medline].
Driscoll SG. Chorioamnionitis: perinatal morbidity and mortality. Pediatr Infect Dis. 1986 Nov-Dec. 5(6 suppl):S273-5. [Medline].
Sultan P, David AL, Fernando R, Ackland GL. Inflammation and epidural-related maternal fever: proposed mechanisms. Anesth Analg. 2016 May. 122(5):1546-53. [Medline].
Martinez-Portilla RJ, Hawkins-Villarreal A, Alvarez-Ponce P, et al. Maternal serum interleukin-6: a non-invasive predictor of histological chorioamnionitis in women with preterm-prelabor rupture of membranes. Fetal Diagn Ther. 2018 Apr 10. 159 (3):579-83. [Medline].
Figueroa R, Garry D, Elimian A. Evaluation of amniotic fluid cytokines in preterm labor and intact membranes. J Matern Fetal Neonatal Med. 2005 Oct. 18(4):241-7. [Medline].
Kacerovsky M, Musilova I, Hornychova H, et al. Bedside assessment of amniotic fluid interleukin-6 in preterm prelabor rupture of membranes. Am J Obstet Gynecol. 2014 Oct. 211(4):385.e1-9. [Medline].
Chaemsaithong P, Romero R, Korzeniewski SJ, et al. A point of care test for interleukin-6 in amniotic fluid in preterm prelabor rupture of membranes: a step toward the early treatment of acute intra-amniotic inflammation/infection. J Matern Fetal Neonatal Med. 2016 Feb. 29 (3):360-7. [Medline].
Kayem G, Goffinet F, Batteux F. Detection of interleukin-6 in vaginal secretions of women with preterm premature rupture of membranes and its association with neonatal infection: a rapid immunochromatographic test. Am J Obstet Gynecol. 2005 Jan. 192(1):140-5. [Medline].
Chaemsaithong P, Romero R, Korzeniewski SJ, et al. A rapid interleukin-6 bedside test for the identification of intra-amniotic inflammation in preterm labor with intact membranes. J Matern Fetal Neonatal Med. 2016 Feb. 29 (3):349-59. [Medline].
Chaiyasit N, Romero R, Chaemsaithong P, et al. Clinical chorioamnionitis at term VIII: a rapid MMP-8 test for the identification of intra-amniotic inflammation. J Perinat Med. 2017 Jul 26. 45(5):539-50. [Medline].
Chaemsaithong P, Romero R, Docheva N, et al. Comparison of rapid MMP-8 and interleukin-6 point-of-care tests to identify intra-amniotic inflammation/infection and impending preterm delivery in patients with preterm labor and intact membranes. J Matern Fetal Neonatal Med. 2018 Jan. 31(2):228-44. [Medline].
Straka M, Dela Cruz W, Blackmon C. Rapid detection of group B streptococcus and Escherichia coli in amniotic fluid using real-time fluorescent PCR. Infect Dis Obstet Gynecol. 2004 Sep-Dec. 12(3-4):109-14. [Medline].
Akers A, Jarzembowski JA, Johnson CT, Lieberman RW, Dalton VK. Examining the relationship between positive mid-gestational fetal fibronectin assays and histological evidence of acute placental inflammation. J Perinat Med. 2007. 35(1):36-42. [Medline].
[Guideline] Verani JR, McGee L, Schrag SJ, for the Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC). Prevention of perinatal group B streptococcal disease--revised guidelines from CDC, 2010. MMWR Recomm Rep. 2010 Nov 19. 59 (RR-10):1-36. [Medline]. [Full Text].
[Guideline] Cagno CK, Pettit JM, Weiss BD. Prevention of perinatal group B streptococcal disease: updated CDC guideline. Am Fam Physician. 2012 Jul 1. 86 (1):59-65. [Medline]. [Full Text].
[Guideline] Perinatal group B streptococcal disease after universal screening recommendations--United States, 2003-2005. MMWR Morb Mortal Wkly Rep. 2007 Jul 20. 56(28):701-5. [Medline].
Elvedi-Gasparovic V, Peter B. Maternal group B streptococcus infection, neonatal outcome and the role of preventive strategies. Coll Antropol. 2008 Mar. 32(1):147-51. [Medline].
Pulver LS, Hopfenbeck MM, Young PC, et al. Continued early onset group B streptococcal infections in the era of intrapartum prophylaxis. J Perinatol. 2009 Jan. 29(1):20-5. [Medline].
Khalil MR, Uldbjerg N, Thorsen PB, Moller JK. Intrapartum PCR assay versus antepartum culture for assessment of vaginal carriage of group B streptococci in a Danish cohort at birth. PLoS One. 2017. 12(7):e0180262. [Medline].
Abdelazim IA. Intrapartum polymerase chain reaction for detection of group B streptococcus colonisation. Aust N Z J Obstet Gynaecol. 2013 Jun. 53(3):236-42. [Medline].
Tanaka K, Iwashita M, Matsushima M, et al. Intrapartum group B streptococcus screening using real-time polymerase chain reaction in Japanese population. J Matern Fetal Neonatal Med. 2016. 29(1):130-4. [Medline].
Shim SS, Romero R, Jun JK. C-reactive protein concentration in vaginal fluid as a marker for intra-amniotic inflammation/infection in preterm premature rupture of membranes. J Matern Fetal Neonatal Med. 2005 Dec. 18(6):417-22. [Medline].
Wiwanitkit V. Maternal C-reactive protein for detection of chorioamnionitis: an appraisal. Infect Dis Obstet Gynecol. 2005 Sep. 13(3):179-81. [Medline].
Wiswell TE, Baumgart S, Gannon CM. No lumbar puncture in the evaluation for early neonatal sepsis: will meningitis be missed?. Pediatrics. 1995 Jun. 95(6):803-6. [Medline].
Sherman MP, Goetzman BW, Ahlfors CE. Tracheal asiration and its clinical correlates in the diagnosis of congenital pneumonia. Pediatrics. 1980 Feb. 65(2):258-63. [Medline].
Manroe BL, Rosenfeld CR, Weinberg AG. The differential leukocyte count in the assessment and outcome of early-onset neonatal group B streptococcal disease. J Pediatr. 1977 Oct. 91(4):632-7. [Medline].
Manroe BL, Weinberg AG, Rosenfeld CR. The neonatal blood count in health and disease. I. Reference values for neutrophilic cells. J Pediatr. 1979 Jul. 95(1):89-98. [Medline].
Cornbleet PJ. Clinical utility of the band count. Clin Lab Med. 2002 Mar. 22(1):101-36. [Medline].
Christensen RD, Henry E, Wiedmeier SE, Stoddard RA, Lambert DK. Low blood neutrophil concentrations among extremely low birth weight neonates: data from a multihospital health-care system. J Perinatol. 2006 Nov. 26(11):682-7. [Medline].
Schelonka RL, Waites KB. Ureaplasma infection and neonatal lung disease. Semin Perinatol. 2007 Feb. 31(1):2-9. [Medline].
Christensen RD. Morphology and concentration of circulating neutrophils in neonates with bacterial sepsis. Pediatr Infect Dis J. 1987 May. 6(5):429-30. [Medline].
Christensen RD, Rothstein G, Anstall HB, Bybee B. Granulocyte transfusions in neonates with bacterial infection, neutropenia, and depletion of mature marrow neutrophils. Pediatrics. 1982 Jul. 70(1):1-6. [Medline].
Benitz WE, Han MY, Madan A. Serial serum C-reactive protein levels in the diagnosis of neonatal infection. Pediatrics. 1998 Oct. 102(4):e41. [Medline].
Ng PC, Li G, Chui KM, et al. Neutrophil CD64 is a sensitive diagnostic marker for early-onset neonatal infection. Pediatr Res. 2004 Nov. 56(5):796-803. [Medline].
Chauhan N, Tiwari S, Jain U. Potential biomarkers for effective screening of neonatal sepsis infections: an overview. Microb Pathog. 2017 Jun. 107:234-42. [Medline].
Simonsen KA, Anderson-Berry AL, Delair SF, Davies HD. Early-onset neonatal sepsis. Clin Microbiol Rev. 2014 Jan. 27(1):21-47. [Medline].
Makhoul IR, Sprecher H, Smolkin T, Sawaid R, Ben-David S, Sujov P, et al. Approach to term neonates born after maternal intrapartum fever and unknown maternal group B Streptococcus status: value of serum C-reactive protein and 16S rRNA gene PCR amplification. Pediatr Infect Dis J. 2007 Nov. 26(11):1064-6. [Medline].
Ohlin A, Backman A, Bjorkqvist M, Molling P, Jurstrand M, Schollin J. Real-time PCR of the 16S-rRNA gene in the diagnosis of neonatal bacteraemia. Acta Paediatr. 2008 Oct. 97(10):1376-80. [Medline].
Midan DA, Abo El Fotoh WMM, El Shalakany AH. The potential role of incorporating real-time PCR and DNA sequencing for amplification and detection of 16S rRNA gene signatures in neonatal sepsis. J Matern Fetal Neonatal Med. 2017 Jun. 30(12):1476-83. [Medline].
Liu CL, Ai HW, Wang WP, et al. Comparison of 16S rRNA gene PCR and blood culture for diagnosis of neonatal sepsis. Arch Pediatr. 2014 Feb. 21(2):162-9. [Medline].
Sherer DM, Spong CY, Salafia CM. Fetal breathing movements within 24 hours of delivery in prematurity are related to histologic and clinical evidence of amnionitis. Am J Perinatol. 1997 Jul. 14(6):337-40. [Medline].
Ghidini A, Salafia CM, Kirn V. Biophysical profile in predicting acute ascending infection in preterm rupture of membranes before 32 weeks. Obstet Gynecol. 2000 Aug. 96(2):201-6. [Medline].
Heller DS, Rimpel LH, Skurnick JH. Does histologic chorioamnionitis correspond to clinical chorioamnionitis?. J Reprod Med. 2008 Jan. 53(1):25-8. [Medline].
Redline RW, Faye-Petersen O, Heller D, Qureshi F, Savell V, Vogler C. Amniotic infection syndrome: nosology and reproducibility of placental reaction patterns. Pediatr Dev Pathol. 2003 Sep-Oct. 6(5):435-48. [Medline].
Lim L, Rozycki HJ. Postnatal SNAP-II scores in neonatal intensive care unit patients: relationship to sepsis, necrotizing enterocolitis, and death. J Matern Fetal Neonatal Med. 2008 Jun. 21(6):415-9. [Medline].
Money N, Newman J, Demissie S, Roth P, Blau J. Anti-microbial stewardship: antibiotic use in well-appearing term neonates born to mothers with chorioamnionitis. J Perinatol. 2017 Dec. 37 (12):1304-9. [Medline].
Jan AI, Ramanathan R, Cayabyab RG. Chorioamnionitis and management of asymptomatic infants ≥35 weeks without empiric antibiotics. Pediatrics. 2017 Jul. 140(1):[Medline].
Berardi A, Buffagni AM, Rossi C, et al. Serial physical examinations, a simple and reliable tool for managing neonates at risk for early-onset sepsis. World J Clin Pediatr. 2016 Nov 8. 5(4):358-64. [Medline].
Puopolo KM, Draper D, Wi S, et al. Estimating the probability of neonatal early-onset infection on the basis of maternal risk factors. Pediatrics. 2011 Nov. 128(5):e1155-63. [Medline].
Escobar GJ, Puopolo KM, Wi S, et al. Stratification of risk of early-onset sepsis in newborns ≥ 34 weeks' gestation. Pediatrics. 2014 Jan. 133(1):30-6. [Medline].
Shakib J, Buchi K, Smith E, Young PC. Management of newborns born to mothers with chorioamnionitis: is it time for a kinder, gentler approach?. Acad Pediatr. 2015 May-Jun. 15(3):340-4. [Medline].
Kuzniewicz MW, Puopolo KM, Fischer A, et al. A quantitative, risk-based approach to the management of neonatal early-onset sepsis. JAMA Pediatr. 2017 Apr 1. 171(4):365-71. [Medline].
Warren S, Garcia M, Hankins C. Impact of neonatal early-onset sepsis calculator on antibiotic use within two tertiary healthcare centers. J Perinatol. 2017 Apr. 37(4):394-7. [Medline].
Baltimore RS. Consequences of prophylaxis for group B streptococcal infections of the neonate. Semin Perinatol. 2007 Feb. 31(1):33-8. [Medline].
Schrag SJ, Hadler JL, Arnold KE, Martell-Cleary P, Reingold A, Schuchat A. Risk factors for invasive, early-onset Escherichia coli infections in the era of widespread intrapartum antibiotic use. Pediatrics. 2006 Aug. 118(2):570-6. [Medline].
Winn HN. Group B streptococcus infection in pregnancy. Clin Perinatol. 2007 Sep. 34(3):387-92. [Medline].
Schrag SJ, Zell ER, Lynfield R. A population-based comparison of strategies to prevent early-onset group B streptococcal disease in neonates. N Engl J Med. 2002 Jul 25. 347(4):233-9. [Medline].
Martingano D, Renson A, Rogoff S, et al. Daily gentamicin using ideal body weight demonstrates lower risk of postpartum endometritis and increased chance of successful outcome compared with traditional 8-hour dosing for the treatment of intrapartum chorioamnionitis. J Matern Fetal Neonatal Med. 2018 Apr 12. 51 (1):1-5. [Medline].
Bond DM, Middleton P, Levett KM, et al. Planned early birth versus expectant management for women with preterm prelabour rupture of membranes prior to 37 weeks' gestation for improving pregnancy outcome. Cochrane Database Syst Rev. 2017 Mar 3. 3:CD004735. [Medline].
Abou El Senoun G, Dowswell T, Mousa HA. Planned home versus hospital care for preterm prelabour rupture of the membranes (PPROM) prior to 37 weeks' gestation [update]. Cochrane Database Syst Rev. 2014 Apr 14. CD008053. [Medline].
Gyamfi-Bannerman C, Thom EA, Blackwell SC, et al, for the NICHD Maternal–Fetal Medicine Units Network. Antenatal betamethasone for women at risk for late preterm delivery. N Engl J Med. 2016 Apr 7. 374(14):1311-20. [Medline].
Saccone G, Berghella V. Antenatal corticosteroids for maturity of term or near term fetuses: systematic review and meta-analysis of randomized controlled trials. BMJ. 2016 Oct 12. 355:i5044. [Medline].
American College of Obstetricians and Gynecologists’ Committee on Obstetric Practice, Society for Maternal–Fetal Medicine. Committee opinion no. 677: antenatal corticosteroid therapy for fetal maturation. Obstet Gynecol. 2016 Oct. 128 (4):e187-94. [Medline].
Society for Maternal-Fetal Medicine (SMFM) Publications Committee. Implementation of the use of antenatal corticosteroids in the late preterm birth period in women at risk for preterm delivery. Am J Obstet Gynecol. 2016 Aug. 215(2):B13-5. [Medline].
Cross SN, Nelson RA, Potter JA, Norwitz ER, Abrahams VM. Magnesium sulfate differentially modulates fetal membrane inflammation in a time-dependent manner. Am J Reprod Immunol. 2018 Apr 30. 200(4):e12861. [Medline].
Schelonka RL, Infante AJ. Neonatal immunology. Semin Perinatol. 1998 Feb. 22(1):2-14. [Medline].
Cohen-Wolkowiez M, Benjamin DK Jr, Capparelli E. Immunotherapy in neonatal sepsis: advances in treatment and prophylaxis. Curr Opin Pediatr. 2009 Apr. 21(2):177-81. [Medline].
Shaw CK, Thapalial A, Shaw P, Malla K. Intravenous immunoglobulins and haematopoietic growth factors in the prevention and treatment of neonatal sepsis: ground reality or glorified myths?. Int J Clin Pract. 2007 Mar. 61(3):482-7. [Medline].
Ohlsson A, Lacy J. Intravenous immunoglobulin for suspected or subsequently proven infection in neonates [update]. Cochrane Database Syst Rev. 2010 Mar 17. 3:CD001239. [Medline].
Castagnola E, Dufour C. Role of G-CSF GM-CSF in the management of infections in preterm newborns: an update. Early Hum Dev. 2014 Sep. 90 Suppl 2:S15-7. [Medline].
Baker CJ, Byington CL, Polin RA, for the Committee on Infectious Diseases, Committee on Fetus and Newborn. Policy statement—Recommendations for the prevention of perinatal group B streptococcal (GBS) disease. Pediatrics. 2011 Sep. 128 (3):611-6. [Medline]. [Full Text].
American College of Obstetricians and Gynecologists Committee on Obstetric Practice. ACOG Committee opinion no. 485: Prevention of early-onset group B streptococcal disease in newborns. Obstet Gynecol. 2011 Apr. 117 (4):1019-27. [Medline].
Money D, Allen VM, Society of Obstetrician and Gynaecologists of Canada. The prevention of early-onset neonatal group B streptococcal disease. J Obstet Gynaecol Can. 2013 Oct. 35 (10):939-51. [Medline]. [Full Text].
Borchardt SM, DeBusscher JH, Tallman PA, et al. Frequency of antimicrobial resistance among invasive and colonizing Group B streptococcal isolates. BMC Infect Dis. 2006 Mar 20. 6:57. [Medline].
Phares CR, Lynfield R, Farley MM, et al. Epidemiology of invasive group B streptococcal disease in the United States, 1999-2005. JAMA. 2008 May 7. 299(17):2056-65. [Medline].
Huang J, Li S, Li L, Wang X, Yao Z, Ye X. Alarming regional differences in prevalence and antimicrobial susceptibility of group B streptococci in pregnant women: A systematic review and meta-analysis. J Glob Antimicrob Resist. 2016 Dec. 7:169-77. [Medline].
Melo SC, Santos NC, Oliveira M, et al. Antimicrobial susceptibility of Streptococcus agalactiae isolated from pregnant women. Rev Inst Med Trop Sao Paulo. 2016 Nov 3. 58:83. [Medline].
Lopez Y, Parra E, Cepas V, et al. Serotype, virulence profile, antimicrobial resistance and macrolide-resistance determinants in Streptococcus agalactiae isolates in pregnant women and neonates in Catalonia, Spain. Enferm Infecc Microbiol Clin. 2017 Oct 10. [Medline].
Matani C, Trezzi M, Matteini A, Catalani C, Messeri D, Catalani C. Streptococcus agalactiae: prevalence of antimicrobial resistance in vaginal and rectal swabs in Italian pregnant women. Infez Med. 2016 Sep 1. 24(3):217-21. [Medline].
Nayak S, Welling J, Burd I. Maternal immunomodulation therapy for prevention of preterm birth and prematurity-related morbidity: The new era of immuno-perinatology. Curr Pharm Des. 2017 Sep 25. [Medline].
Dangor Z, Lala SG, Kwatra G, Madhi SA. Group B Streptococcus: developing a correlate of protection for a vaccine against neonatal infections. Curr Opin Infect Dis. 2016 Jun. 29(3):262-7. [Medline].
Stoll BJ, Hansen NI, Higgins RD. Very low birth weight preterm infants with early onset neonatal sepsis: the predominance of gram-negative infections continues in the National Institute of Child Health and Human Development Neonatal Research Network, 2002-2003. Pediatr Infect Dis J. 2005 Jul. 24(7):635-9. [Medline].
Hollier L, Wendel GD, ed. Infectious diseases in pregnancy. Clin Perinatol. 2005. 32(3):523-824. [Full Text].
Romero R, Espinoza J, Goncalves LF, Kusanovic JP, Friel L, Hassan S. The role of inflammation and infection in preterm birth. Semin Reprod Med. 2007 Jan. 25(1):21-39. [Medline].
Romero R, Gotsch F, Pineles B, Kusanovic JP. Inflammation in pregnancy: its roles in reproductive physiology, obstetrical complications, and fetal injury. Nutr Rev. 2007 Dec. 65(12 Pt 2):S194-202. [Medline].
Malaeb S, Dammann O. Fetal inflammatory response and brain injury in the preterm newborn. J Child Neurol. 2009 Sep. 24(9):1119-26. [Medline].
Hakansson S, Kallen K. High maternal body mass index increases the risk of neonatal early onset group B streptococcal disease. Acta Paediatr. 2008 Oct. 97(10):1386-9. [Medline].
Swadpanich U, Lumbiganon P, Prasertcharoensook W, Laopaiboon M. Antenatal lower genital tract infection screening and treatment programs for preventing preterm delivery. Cochrane Database Syst Rev. 2008 Apr 16. CD006178. [Medline].
McDonald HM, Brocklehurst P, Gordon A. Antibiotics for treating bacterial vaginosis in pregnancy. Cochrane Database Syst Rev. 2007 Jan 24. CD000262. [Medline].
Kabiru W, Raynor BD. Obstetric outcomes associated with increase in BMI category during pregnancy. Am J Obstet Gynecol. 2004 Sep. 191(3):928-32. [Medline].
Raatikainen K, Heiskanen N, Heinonen S. Transition from overweight to obesity worsens pregnancy outcome in a BMI-dependent manner. Obesity (Silver Spring). 2006 Jan. 14(1):165-71. [Medline].
Joy SD, Zhao Y, Mercer BM, et al. Latency and infectious complications after preterm premature rupture of membranes: impact of body mass index. Am J Obstet Gynecol. 2009 Dec. 201(6):600.e1-5. [Medline].
Otsuki K, Yoda A, Saito H. Amniotic fluid lactoferrin in intrauterine infection. Placenta. 1999 Mar-Apr. 20(2-3):175-9. [Medline].
King AE, Critchley HO, Kelly RW. Innate immune defences in the human endometrium. Reprod Biol Endocrinol. 2003 Nov 28. 1:116. [Medline].
Reid G, Burton J. Use of Lactobacillus to prevent infection by pathogenic bacteria. Microbes Infect. 2002 Mar. 4(3):319-24. [Medline].
Matorras R, Garcia Perea A, Omenaca F, Usandizaga JA, Nieto A, Herruzo R. Group B streptococcus and premature rupture of membranes and preterm delivery. Gynecol Obstet Invest. 1989. 27(1):14-8. [Medline].
Sanchez PJ, Regan JA. Vertical transmission of Ureaplasma urealyticum from mothers to preterm infants. Pediatr Infect Dis J. 1990 Jun. 9(6):398-401. [Medline].
Spiegel CA. Bacterial vaginosis. Clin Microbiol Rev. 1991 Oct. 4(4):485-502. [Medline].
Donders GG, Vereecken A, Bosmans E, Dekeersmaecker A, Salembier G, Spitz B. Definition of a type of abnormal vaginal flora that is distinct from bacterial vaginosis: aerobic vaginitis. BJOG. 2002 Jan. 109 (1):34-43. [Medline].
Naeye RL, Ross S. Coitus and chorioamnionitis: a prospective study. Early Hum Dev. 1982 Jan. 6(1):91-7. [Medline].
Yost NP, Owen J, Berghella V. Effect of coitus on recurrent preterm birth. Obstet Gynecol. 2006 Apr. 107(4):793-7. [Medline].
Jones HE, Harris KA, Azizia M, et al. Differing prevalence and diversity of bacterial species in fetal membranes from very preterm and term labor. PLoS One. 2009 Dec 8. 4(12):e8205. [Medline]. [Full Text].
Edwards RK, Novak-Weekley SM, Koty PP, Davis T, Leeds LJ, Jordan JA. Rapid group B streptococci screening using a real-time polymerase chain reaction assay. Obstet Gynecol. 2008 Jun. 111(6):1335-41. [Medline].
Karpuch J, Goldberg M, Kohelet D. Neonatal bacteremia. A 4-year prospective study. Isr J Med Sci. 1983 Nov. 19(11):963-6. [Medline].
Gilstrap LC 3rd, Leveno KJ, Cox SM, Burris JS, Mashburn M, Rosenfeld CR. Intrapartum treatment of acute chorioamnionitis: impact on neonatal sepsis. Am J Obstet Gynecol. 1988 Sep. 159 (3):579-83. [Medline].
Sundaram V, Kumar P, Dutta S, et al. Blood culture confirmed bacterial sepsis in neonates in a North Indian tertiary care center: changes over the last decade. Jpn J Infect Dis. 2009 Jan. 62(1):46-50. [Medline].
Berenson AB, Wiemann CM, Wilkinson GS. Perinatal morbidity associated with violence experienced by pregnant women. Am J Obstet Gynecol. 1994 Jun. 170(6):1760-6; discussion 1766-9. [Medline].
Turner BJ, McKee LJ, Silverman NS. Prenatal care and birth outcomes of a cohort of HIV-infected women. J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Jul. 12(3):259-67. [Medline].
Scholl TO. High third-trimester ferritin concentration: associations with very preterm delivery, infection, and maternal nutritional status. Obstet Gynecol. 1998 Aug. 92(2):161-6. [Medline].
Romero R, Chaiworapongsa T, Espinoza J. Micronutrients and intrauterine infection, preterm birth and the fetal inflammatory response syndrome. J Nutr. 2003 May. 133(5 suppl 2):1668S-73S. [Medline].
St Geme JW Jr, Murray DL, Carter J, et al. Perinatal bacterial infection after prolonged rupture of amniotic membranes: an analysis of risk and management. J Pediatr. 1984 Apr. 104 (4):608-13. [Medline].
Rickert VI, Wiemann CM, Hankins GD, McKee JM, Berenson AB. Prevalence and risk factors of chorioamnionitis among adolescents. Obstet Gynecol. 1998 Aug. 92(2):254-7. [Medline].
O'Brien RF. Bacterial vaginosis: many questions--any answers?. Curr Opin Pediatr. 2005 Aug. 17(4):473-9. [Medline].
Gaudet LM, Flavin M, Islam O, Smith GN. Diffusion MRI brain findings in neonates exposed to chorioamnionitis: a case series. J Obstet Gynaecol Can. 2009 Jun. 31(6):497-503. [Medline].
Wu YW, Croen LA, Torres AR, Van De Water J, Grether JK, Hsu NN. Interleukin-6 genotype and risk for cerebral palsy in term and near-term infants. Ann Neurol. 2009 Nov. 66(5):663-70. [Medline].
Getahun D, Strickland D, Zeiger RS, et al. Effect of chorioamnionitis on early childhood asthma. Arch Pediatr Adolesc Med. 2010 Feb. 164(2):187-92. [Medline].
Ito M, Nakashima A, Hidaka T, et al. A role for IL-17 in induction of an inflammation at the fetomaternal interface in preterm labour. J Reprod Immunol. 2010 Jan. 84(1):75-85. [Medline].
Redline R, Minich N, Taylor H, Hack M. Placental lesions as predictors of cerebral palsy and abnormal neurocognitive function at school age in extremely low birth weight infants (Pediatr Dev Pathol</i>. 2007 Mar 22. 1. [Medline].
Viscardi RM, Muhumuza CK, Rodriguez A, et al. Inflammatory markers in intrauterine and fetal blood and cerebrospinal fluid compartments are associated with adverse pulmonary and neurologic outcomes in preterm infants. Pediatr Res. 2004 Jun. 55(6):1009-17. [Medline].
Kasper DC, Mechtler TP, Reischer GH, et al. The bacterial load of Ureaplasma parvum in amniotic fluid is correlated with an increased intrauterine inflammatory response. Diagn Microbiol Infect Dis. 2010 Mar 4. [Medline].
Namba F, Hasegawa T, Nakayama M, et al. Placental features of chorioamnionitis colonized with Ureaplasma species in preterm delivery. Pediatr Res. 2010 Feb. 67(2):166-72. [Medline].
Jenkins DD, Wiest DB, Mulvihill DM, et al. Fetal and neonatal effects of N-acetylcysteine when used for neuroprotection in maternal chorioamnionitis. J Pediatr. 2016 Jan. 168:67-76.e6. [Medline].
Adams-Chapman I, Stoll BJ. Neonatal infection and long-term neurodevelopmental outcome in the preterm infant. Curr Opin Infect Dis. 2006 Jun. 19(3):290-7. [Medline].
Ragouilliaux CJ, Keeney SE, Hawkins HK, Rowen JL. Maternal factors in extremely low birth weight infants who develop spontaneous intestinal perforation. Pediatrics. 2007 Dec. 120(6):e1458-64. [Medline].
Dulay AT, Buhimschi IA, Zhao G, et al. Nucleated red blood cells are a direct response to mediators of inflammation in newborns with early-onset neonatal sepsis. Am J Obstet Gynecol. 2008 Apr. 198(4):426.e1-9. [Medline].
Redline RW. Elevated circulating fetal nucleated red blood cells and placental pathology in term infants who develop cerebral palsy. Hum Pathol. 2008 Sep. 39(9):1378-84. [Medline].
Buhimschi CS, Bhandari V, Han YW, et al. Using proteomics in perinatal and neonatal sepsis: hopes and challenges for the future. Curr Opin Infect Dis. 2009 Jun. 22(3):235-43. [Medline].
DiGiulio DB, Romero R, Kusanovic JP, et al. Prevalence and diversity of microbes in the amniotic fluid, the fetal inflammatory response, and pregnancy outcome in women with preterm pre-labor rupture of membranes. Am J Reprod Immunol. 2010 Jul 1. 64 (1):38-57. [Medline].
Romero R, Kusanovic JP, Gotsch F, Erez O, Vaisbuch E, Mazaki-Tovi S. Isobaric labeling and tandem mass spectrometry: a novel approach for profiling and quantifying proteins differentially expressed in amniotic fluid in preterm labor with and without intra-amniotic infection/inflammation. J Matern Fetal Neonatal Med. 2010 Apr. 23(4):261-80. [Medline].
Speer CP. Pulmonary inflammation and bronchopulmonary dysplasia. J Perinatol. 2006 May. 26 Suppl 1:S57-62; discussion S63-4. [Medline].
Ryan RM, Ahmed Q, Lakshminrusimha S. Inflammatory mediators in the immunobiology of bronchopulmonary dysplasia. Clin Rev Allergy Immunol. 2008 Apr. 34(2):174-90. [Medline].
Tran SH, Cheng YW, Kaimal AJ, Caughey AB. Length of rupture of membranes in the setting of premature rupture of membranes at term and infectious maternal morbidity. Am J Obstet Gynecol. 2008 Jun. 198(6):700.e1-5. [Medline].
Bender L, Thaarup J, Varming K, Krarup H, Ellermann-Eriksen S, Ebbesen F. Early and late markers for the detection of early-onset neonatal sepsis. Dan Med Bull. 2008 Nov. 55(4):219-23. [Medline].
Cetinkaya M, Ozkan H, Koksal N, Celebi S, Hacimustafaoglu M. Comparison of serum amyloid A concentrations with those of C-reactive protein and procalcitonin in diagnosis and follow-up of neonatal sepsis in premature infants. J Perinatol. 2009 Mar. 29(3):225-31. [Medline].
Xiao Y, Griffin MP, Lake DE, Moorman JR. Nearest-neighbor and logistic regression analyses of clinical and heart rate characteristics in the early diagnosis of neonatal sepsis. Med Decis Making. 2010 Mar-Apr. 30(2):258-66. [Medline].
Paules C, Moreno E, Gonzales A, Fabre E, Gonzalez de Aguero R, Oros D. Amniotic fluid sludge as a marker of intra-amniotic infection and histological chorioamnionitis in cervical insufficiency: a report of four cases and literature review. J Matern Fetal Neonatal Med. 2016. 29 (16):2681-4. [Medline].
Aina-Mumuney AJ, Althaus JE, Henderson JL, Blakemore MC, Johnson EA, Graham EM. Intrapartum electronic fetal monitoring and the identification of systemic fetal inflammation. J Reprod Med. 2007 Sep. 52(9):762-8. [Medline].
Vallejo MC, Kaul B, Adler LJ. Chorioamnionitis, not epidural analgesia, is associated with maternal fever during labour. Can J Anaesth. 2001 Dec. 48(11):1122-6. [Medline].
Alexander JM. Epidural analgesia for labor pain and its relationship to fever. Clin Perinatol. 2005 Sep. 32(3):777-87. [Medline].
Impey L, Greenwood C, MacQuillan K, Reynolds M, Sheil O. Fever in labour and neonatal encephalopathy: a prospective cohort study. BJOG. 2001 Jun. 108(6):594-7. [Medline].
Andrews WW, Hauth JC, Cliver SP, Savage K, Goldenberg RL. Randomized clinical trial of extended spectrum antibiotic prophylaxis with coverage for Ureaplasma urealyticum to reduce post-cesarean delivery endometritis. Obstet Gynecol. 2003 Jun. 101(6):1183-9. [Medline].
Matlow A, Th'ng C, Kovach D, Quinn P, Dunn M, Wang E. Susceptibilities of neonatal respiratory isolates of Ureaplasma urealyticum to antimicrobial agents. Antimicrob Agents Chemother. 1998 May. 42(5):1290-2. [Medline].
Cakar E, Cakar SE, Tasan HA, et al. Diagnostic and prognostic value of presepsin for subclinical chorioamnionitis in pregnancies between 23-28 week with preterm premature rupture of the membranes. Balkan Med J. 2016 Nov. 33 (6):668-674. [Medline].
Volante E, Moretti S, Pisani F. Early diagnosis of bacterial infection in the neonate. J Matern Fetal Neonatal Med. 2004 Nov. 16 Suppl 2:13-6. [Medline].
Daniels J, Gray J, Pattison H, et al. Rapid testing for group B streptococcus during labour: a test accuracy study with evaluation of acceptability and cost-effectiveness. Health Technol Assess. 2009 Sep. 13(42):1-154, iii-iv. [Medline].
Benitz WE, Gould JB, Druzin ML. Preventing early-onset group B streptococcal sepsis: strategy development using decision analysis. Pediatrics. 1999 Jun. 103(6):e76. [Medline].
Akker-van Marle ME, Rijnders ME, Dommelen P, et al. Cost-effectiveness of different treatment strategies with intrapartum antibiotic prophylaxis to prevent early-onset group B streptococcal disease. BJOG. 2005 Jun. 112(6):820-6. [Medline].
Visser VE, Hall RT. Urine culture in the evaluation of suspected neonatal sepsis. J Pediatr. 1979 Apr. 94(4):635-8. [Medline].
Sherman MP, Chance KH, Goetzman BW. Gram's stains of tracheal secretions predict neonatal bacteremia. Am J Dis Child. 1984 Sep. 138(9):848-50. [Medline].
Ng PC, Li G, Chui KM, et al. Quantitative measurement of monocyte HLA-DR expression in the identification of early-onset neonatal infection. Biol Neonate. 2006. 89(2):75-81. [Medline].
Mishra UK, Jacobs SE, Doyle LW, Garland SM. Newer approaches to the diagnosis of early onset neonatal sepsis. Arch Dis Child Fetal Neonatal Ed. 2006 May. 91(3):F208-12. [Medline].
Brozanski BS, Jones JG, Krohn MJ, Jordan JA. Use of polymerase chain reaction as a diagnostic tool for neonatal sepsis can result in a decrease in use of antibiotics and total neonatal intensive care unit length of stay. J Perinatol. 2006 Nov. 26(11):688-92. [Medline].
Buchanan SL, Crowther CA, Levett KM, Middleton P, Morris J. Planned early birth versus expectant management for women with preterm prelabour rupture of membranes prior to 37 weeks' gestation for improving pregnancy outcome. Cochrane Database Syst Rev. 2010 Mar 17. 3:CD004735. [Medline].
Abou El Senoun G, Dowswell T, Mousa HA. Planned home versus hospital care for preterm prelabour rupture of the membranes (PPROM) prior to 37 weeks' gestation. Cochrane Database Syst Rev. 2010 Apr 14. 4:CD008053. [Medline].
Amstey MS, Gibbs RS. Is penicillin G a better choice than ampicillin for prophylaxis of neonatal group B streptococcal infections?. Obstet Gynecol. 1994 Dec. 84(6):1058-9. [Medline].
Apgar BS, Greenberg G, Yen G. Prevention of group B streptococcal disease in the newborn. Am Fam Physician. 2005 Mar 1. 71(5):903-10. [Medline].
Alarcon A, Pena P, Salas S, et al. Neonatal early onset Escherichia coli sepsis: trends in incidence and antimicrobial resistance in the era of intrapartum antimicrobial prophylaxis. Pediatr Infect Dis J. 2004 Apr. 23(4):295-9. [Medline].
Gibbs RS, Schrag S, Schuchat A. Perinatal infections due to group B streptococci. Obstet Gynecol. 2004 Nov. 104(5 Pt 1):1062-76. [Medline].
Suri M, Harrison L, Van de Ven C, Cairo MS. Immunotherapy in the prophylaxis and treatment of neonatal sepsis. Curr Opin Pediatr. 2003 Apr. 15(2):155-60. [Medline].
Boggess KA. Pathophysiology of preterm birth: emerging concepts of maternal infection. Clin Perinatol. 2005 Sep. 32(3):561-9. [Medline].
Shennan A, Crawshaw S, Briley A. A randomised controlled trial of metronidazole for the prevention of preterm birth in women positive for cervicovaginal fetal fibronectin: the PREMET Study. BJOG. 2006 Jan. 113(1):65-74. [Medline].
Berger A, Witt A, Haiden N, et al. Intrauterine infection with Ureaplasma species is associated with adverse neuromotor outcome at 1 and 2 years adjusted age in preterm infants. J Perinat Med. 2009. 37(1):72-8. [Medline].
Bayraktar MR, Ozerol IH, Gucluer N, Celik O. Prevalence and antibiotic susceptibility of Mycoplasma hominis and Ureaplasma urealyticum in pregnant women. Int J Infect Dis. 2010 Feb. 14(2):e90-5. [Medline].
Kartali G, Tzelepi E, Pournaras S, et al. Outbreak of infections caused by Enterobacter cloacae producing the integron-associated beta-lactamase IBC-1 in a neonatal intensive care unit of a Greek hospital. Antimicrob Agents Chemother. 2002 May. 46(5):1577-80. [Medline]. [Full Text].
Young TE, Mangum B. Antimicrobials. NEOFAX 2009. 22nd Edition. Montvale, NJ: Thomson Reuters; 2009. 1-89.
ACOG Statement. ACOG practice bulletin. Premature rupture of membranes. Clinical management guidelines for obstetrician-gynecologists. Number 1, June 1998. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 1998 Oct. 63 (1):75-84. [Medline].
Alanen A. Polymerase chain reaction in the detection of microbes in amniotic fluid. Ann Med. 1998 Jun. 30(3):288-95. [Medline].
Andrews WW, Cliver SP, Biasini F, et al. Early preterm birth: association between in utero exposure to acute inflammation and severe neurodevelopmental disability at 6 years of age. Am J Obstet Gynecol. 2008 Apr. 198(4):466.e1-466.e11. [Medline].
Badri MS, Zawaneh S, Cruz AC. Rectal colonization with group B streptococcus: relation to vaginal colonization of pregnant women. J Infect Dis. 1977 Feb. 135(2):308-12. [Medline].
Benitz WE, Gould JB, Druzin ML. Risk factors for early-onset group B streptococcal sepsis: estimation of odds ratios by critical literature review. Pediatrics. 1999 Jun. 103(6):e77. [Medline].
Berger C, Uehlinger J, Ghelfi D. Comparison of C-reactive protein and white blood cell count with differential in neonates at risk for septicemia. Eur J Pediatr. 1995 Feb. 154(2):138-44. [Medline].
Bint AJ, Hill D. Bacteriuria of pregnancy--an update on significance, diagnosis and management. J Antimicrob Chemother. 1994 May. 33 Suppl A:93-7. [Medline].
Boggess KA, Trevett TN, Madianos PN. Use of DNA hybridization to detect vaginal pathogens associated with bacterial vaginosis among asymptomatic pregnant women. Am J Obstet Gynecol. 2005 Sep. 193(3 Pt 1):752-6. [Medline].
Brocklehurst P. Infection and preterm delivery. BMJ. 1999 Feb 27. 318(7183):548-9. [Medline].
Carey JC, Klebanoff MA, Hauth JC. Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. N Engl J Med. 2000 Feb 24. 342(8):534-40. [Medline].
Christensen RD, Rothstein G, Hill HR. Fatal early onset group B streptococcal sepsis with normal leukocyte counts. Pediatr Infect Dis. 1985 May-Jun. 4(3):242-5. [Medline].
Churgay CA, Smith MA, Blok B. Maternal fever during labor--what does it mean?. J Am Board Fam Pract. 1994 Jan-Feb. 7(1):14-24. [Medline].
Dashe JS, Rogers BB, McIntire DD. Epidural analgesia and intrapartum fever: placental findings. Obstet Gynecol. 1999 Mar. 93(3):341-4. [Medline].
Dobson SR, Isaacs D, Wilkinson AR. Reduced use of surface cultures for suspected neonatal sepsis and surveillance. Arch Dis Child. 1992 Jan. 67(1 Spec No):44-7. [Medline].
Dudley DJ. Immunoendocrinology of preterm labor: the link between corticotropin-releasing hormone and inflammation. Am J Obstet Gynecol. 1999 Jan. 180(1 Pt 3):S251-6. [Medline].
Espinoza J, Chaiworapongsa T, Romero R. Antimicrobial peptides in amniotic fluid: defensins, calprotectin and bacterial/permeability-increasing protein in patients with microbial invasion of the amniotic cavity, intra-amniotic inflammation, preterm labor and premature rupture of membranes. J Matern Fetal Neonatal Med. 2003 Jan. 13(1):2-21. [Medline].
Garcia-Prats JA, Cooper TR, Schneider VF. Rapid detection of microorganisms in blood cultures of newborn infants utilizing an automated blood culture system. Pediatrics. 2000 Mar. 105(3 Pt 1):523-7. [Medline].
Garite TJ, Freeman RK. Chorioamnionitis in the preterm gestation. Obstet Gynecol. 1982 May. 59(5):539-45. [Medline].
Gibbs RS, Davies JK, McDuffie RS Jr. Chronic intrauterine infection and inflammation in the preterm rabbit, despite antibiotic therapy. Am J Obstet Gynecol. 2002 Feb. 186(2):234-9. [Medline].
Gibbs RS, Duff P. Progress in pathogenesis and management of clinical intraamniotic infection. Am J Obstet Gynecol. 1991 May. 164(5 Pt 1):1317-26. [Medline].
Goldenberg RL, Hauth JC, Andrews WW. Intrauterine infection and preterm delivery. N Engl J Med. 2000 May 18. 342(20):1500-7. [Medline].
Goldenberg RL, Mercer BM, Miodovnik M. Plasma ferritin, premature rupture of membranes, and pregnancy outcome. Am J Obstet Gynecol. 1998 Dec. 179(6 Pt 1):1599-604. [Medline].
Goldenberg RL, Mwatha A, Read JS. The HPTN 024 Study: the efficacy of antibiotics to prevent chorioamnionitis and preterm birth. Am J Obstet Gynecol. 2006 Mar. 194(3):650-61. [Medline].
Gomez R, Ghezzi F, Romero R. Premature labor and intra-amniotic infection. Clinical aspects and role of the cytokines in diagnosis and pathophysiology. Clin Perinatol. 1995 Jun. 22(2):281-342. [Medline].
Gonzalez-Bosquet E, Cerqueira MJ, Dominguez C. Amniotic fluid glucose and cytokines values in the early diagnosis of amniotic infection in patients with preterm labor and intact membranes. J Matern Fetal Med. 1999 Jul-Aug. 8(4):155-8. [Medline].
Hachey WE, Wiswell TE. Limitations in the usefulness of urine latex particle agglutination tests and hematologic measurements in diagnosing neonatal sepsis during the first week of life. J Perinatol. 1992 Sep. 12(3):240-5. [Medline].
Hauth JC, Gilstrap LC 3d, Hankins GD. Term maternal and neonatal complications of acute chorioamnionitis. Obstet Gynecol. 1985 Jul. 66(1):59-62. [Medline].
Heighton BL, Halpren SH. The effects of epidural analgesia on labor, maternal, and neonatal outcomes: a systematic review. Am J Obstet Gynecol. 2002. 186(5 Suppl Nature):S69-77.
Hemming VG, McCloskey DW, Hill HR. Pneumonia in the neonate associated with group B streptococcal septicemia. Am J Dis Child. 1976 Nov. 130(11):1231-3. [Medline].
Hillier SL, Martius J, Krohn M. A case-control study of chorioamnionic infection and histologic chorioamnionitis in prematurity. N Engl J Med. 1988 Oct 13. 319(15):972-8. [Medline].
Hussey MJ, Levy ES, Pombar X. Evaluating rapid diagnostic tests of intra-amniotic infection: Gram stain, amniotic fluid glucose level, and amniotic fluid to serum glucose level ratio. Am J Obstet Gynecol. 1998 Sep. 179(3 Pt 1):650-6. [Medline].
Ismail MA, Zinaman MJ, Lowensohn RI. The significance of C-reactive protein levels in women with premature rupture of membranes. Am J Obstet Gynecol. 1985 Feb 15. 151(4):541-4. [Medline].
Johnson CE, Whitwell JK, Pethe K. Term newborns who are at risk for sepsis: are lumbar punctures necessary?. Pediatrics. 1997 Apr. 99(4):e10. [Medline].
Joseph TA, Pyati SP, Jacobs N. Neonatal early-onset Escherichia coli disease. The effect of intrapartum ampicillin. Arch Pediatr Adolesc Med. 1998 Jan. 152(1):35-40. [Medline].
Kaftan H, Kinney JS. Early onset neonatal bacterial infections. Semin Perinatol. 1998 Feb. 22(1):15-24. [Medline].
Kurlat I, Stoll BJ, McGowan JE Jr. Time to positivity for detection of bacteremia in neonates. J Clin Microbiol. 1989 May. 27(5):1068-71. [Medline].
Maeda K, Matsuzaki N, Fuke S. Value of the maternal interleukin 6 level for determination of histologic chorioamnionitis in preterm delivery. Gynecol Obstet Invest. 1997. 43(4):225-31. [Medline].
Mangurten HH, Angst DB, See C, Boyle D, Beckman S. Professional liability in a neonatal intensive care unit: a review of 20 years' experience. J Perinatol. 2000 Jun. 20(4):244-8. [Medline].
Mercer BM, Lewis R. Preterm labor and preterm premature rupture of the membranes. Diagnosis and management. Infect Dis Clin North Am. 1997 Mar. 11(1):177-201. [Medline].
Miura E, Procianoy RS, Bittar C. A randomized, double-masked, placebo-controlled trial of recombinant granulocyte colony-stimulating factor administration to preterm infants with the clinical diagnosis of early-onset sepsis. Pediatrics. 2001 Jan. 107(1):30-5. [Medline].
Moore SE, Cole TJ, Collinson AC. Prenatal or early postnatal events predict infectious deaths in young adulthood in rural Africa. Int J Epidemiol. 1999 Dec. 28(6):1088-95. [Medline].
Murtha AP, Greig PC, Jimmerson CE. Maternal serum interleukin-6 concentrations in patients with preterm premature rupture of membranes and evidence of infection. Am J Obstet Gynecol. 1996 Oct. 175(4 Pt 1):966-9. [Medline].
Nasef N, Shabaan AE, Schurr P, Iaboni D, Choudhury J, Church P, et al. Effect of clinical and histological chorioamnionitis on the outcome of preterm infants. Am J Perinatol. 2013 Jan. 30(1):59-68. [Medline].
Ohlsson A, Lacy JB. Intravenous immunoglobulin for suspected or subsequently proven infection in neonates. Cochrane Database Syst Rev. 2004. CD001239. [Medline].
Philip J, Alexander JM, Sharma SK. Epidural analgesia during labor and maternal fever. Anesthesiology. 1999 May. 90(5):1271-5. [Medline].
Pourcyrous M, Bada HS, Korones SB. Significance of serial C-reactive protein responses in neonatal infection and other disorders. Pediatrics. 1993 Sep. 92(3):431-5. [Medline].
Puopolo KM. Bacterial and fungal infections. In: Cloherty JP, Eichenwald EC, Stark AR, eds. Manual of Neonatal Care. 5th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2004. 287-313.
Schmutz N, Henry E, Jopling J, Christensen RD. Expected ranges for blood neutrophil concentrations of neonates: the Manroe and Mouzinho charts revisited. J Perinatol. 2008 Apr. 28(4):275-81. [Medline].
Schuchat A, Zywicki SS, Dinsmoor MJ. Risk factors and opportunities for prevention of early-onset neonatal sepsis: a multicenter case-control study. Pediatrics. 2000 Jan. 105(1 Pt 1):21-6. [Medline].
Seaward PG, Hannah ME, Myhr TL. International multicenter term PROM study: evaluation of predictors of neonatal infection in infants born to patients with premature rupture of membranes at term. Premature Rupture of the Membranes. Am J Obstet Gynecol. 1998 Sep. 179(3 Pt 1):635-9. [Medline].
Seo K, McGregor JA, French JI. Preterm birth is associated with increased risk of maternal and neonatal infection. Obstet Gynecol. 1992 Jan. 79(1):75-80. [Medline].
Sherman MP. Macrophage function in bacterial and fungal infections of newborns. In: Lipscomb MF, Russell SW, eds. Lung macrophages and dendritic cells. Lung Biology in Health and Disease Series. Vol 102. New York, NY:. Marcel Dekker. 1997:409-436.
Smulian JC, Shen-Schwarz S, Vintzileos AM. Clinical chorioamnionitis and histologic placental inflammation. Obstet Gynecol. 1999 Dec. 94(6):1000-5. [Medline].
Smulian JC, Vintzileos AM, Lai YL. Maternal chorioamnionitis and umbilical vein interleukin-6 levels for identifying early neonatal sepsis. J Matern Fetal Med. 1999 May-Jun. 8(3):88-94. [Medline].
Sreenan C, Osiovich H. Myeloid colony-stimulating factors: use in the newborn. Arch Pediatr Adolesc Med. 1999 Sep. 153(9):984-8. [Medline].
Stoll BJ, Hansen N, Fanaroff AA. Changes in pathogens causing early-onset sepsis in very-low-birth- weight infants. N Engl J Med. 2002 Jul 25. 347(4):240-7. [Medline].
Stoll BJ, Holman RC, Schuchat A. Decline in sepsis-associated neonatal and infant deaths in the United States, 1979 through 1994. Pediatrics. 1998 Aug. 102(2):e18. [Medline].
Teichmann AT, Arendt P, Speer CP. Premature rupture of the membranes and amniotic infections--the significance of laboratory tests. Eur J Obstet Gynecol Reprod Biol. 1990 Mar. 34(3):217-22. [Medline].
Terrone DA, Rinehart BK, Einstein MH. Neonatal sepsis and death caused by resistant Escherichia coli: possible consequences of extended maternal ampicillin administration. Am J Obstet Gynecol. 1999 Jun. 180(6 Pt 1):1345-8. [Medline].
Towers CV, Carr MH, Padilla G. Potential consequences of widespread antepartal use of ampicillin. Am J Obstet Gynecol. 1998 Oct. 179(4):879-83. [Medline].
Vollman JH, Smith WL, Ballard ET. Early onset group B streptococcal disease: clinical, roentgenographic, and pathologic features. J Pediatr. 1976 Aug. 89(2):199-203. [Medline].
Wolach B. Neonatal sepsis: pathogenesis and supportive therapy. Semin Perinatol. 1997 Feb. 21(1):28-38. [Medline].
Yoon BH, Jun JK, Romero R. Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha), neonatal brain white matter lesions, and cerebral palsy. Am J Obstet Gynecol. 1997 Jul. 177(1):19-26. [Medline].
Yoon BH, Romero R, Lim JH. The clinical significance of detecting Ureaplasma urealyticum by the polymerase chain reaction in the amniotic fluid of patients with preterm labor. Am J Obstet Gynecol. 2003 Oct. 189(4):919-24. [Medline].
Yoon BH, Romero R, Shim JY. C-reactive protein in umbilical cord blood: a simple and widely available clinical method to assess the risk of amniotic fluid infection and funisitis. J Matern Fetal Neonatal Med. 2003 Aug. 14(2):85-90. [Medline].
Yoon BH, Yang SH, Jun JK. Maternal blood C-reactive protein, white blood cell count, and temperature in preterm labor: a comparison with amniotic fluid white blood cell count. Obstet Gynecol. 1996 Feb. 87(2):231-7. [Medline].
Hassell KJ, Ezzati M, Alonso-Alconada D, Hausenloy DJ, Robertson NJ. New horizons for newborn brain protection: enhancing endogenous neuroprotection. Arch Dis Child Fetal Neonatal Ed. 2015 Nov. 100 (6):F541-52. [Medline].
Taguchi A, Yamashita A, Kawana K, et al. Recent progress in therapeutics for inflammation-associated preterm birth: a review. Reprod Sci. 2015 Dec 1. [Medline].
Hakansson S, Kallen K, Bullarbo M, et al. Real-time PCR-assay in the delivery suite for determination of group B streptococcal colonization in a setting with risk-based antibiotic prophylaxis. J Matern Fetal Neonatal Med. 2014 Mar. 27 (4):328-32. [Medline].
Di Renzo GC, Melin P, Berardi A, et al. Intrapartum GBS screening and antibiotic prophylaxis: a European consensus conference. J Matern Fetal Neonatal Med. 2015 May. 28 (7):766-82. [Medline].
Jackson CM, Wells CB, Tabangin ME, Meinzen-Derr J, Jobe AH, Chougnet CA. Pro-inflammatory immune responses in leukocytes of premature infants exposed to maternal chorioamnionitis or funisitis. Pediatr Res. 2016 Dec 14. [Medline].
Stranak Z, Feyereisl J, Korcek P, Feyereislova S, Krofta L. Procalcitonin is more likely to be released by the fetus rather than placental tissue during chorioamnionitis. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016 Dec. 160 (4):499-502. [Medline].
Laughon M, Allred EN, Bose C, et al, for the ELGAN Study Investigators. Patterns of respiratory disease during the first 2 postnatal weeks in extremely premature infants. Pediatrics. 2009 Apr. 123(4):1124-31. [Medline].
Thomas W, Speer CP. Chorioamnionitis is essential in the evolution of bronchopulmonary dysplasia--the case in favour. Paediatr Respir Rev. 2014 Mar. 15(1):49-52. [Medline].
Lacaze-Masmonteil T. That chorioamnionitis is a risk factor for bronchopulmonary dysplasia--the case against. Paediatr Respir Rev. 2014 Mar. 15(1):53-5. [Medline].
Kusanovic JP, Romero R, Martinovic C, et al. Transabdominal collection of amniotic fluid "sludge" and identification of Candida albicans intra-amniotic infection. J Matern Fetal Neonatal Med. 2018 May. 31 (10):1279-84. [Medline].
Smulian JC, Bhandari V, Vintzileos AM, et al. Intrapartum fever at term: serum and histologic markers of inflammation. Am J Obstet Gynecol. 2003 Jan. 188(1):269-74. [Medline].
Kasdorf E, Perlman JM. Hyperthermia, inflammation, and perinatal brain injury. Pediatr Neurol. 2013 Jul. 49(1):8-14. [Medline].

Media Gallery

of 0

Author

Fayez M Bany-Mohammed, MD HS Clinical Professor of Pediatrics, Program Director, Neonatal-Perinatal Medicine Fellowship Program, Department of Pediatrics, Division of Neonatology, University of California, Irvine, School of Medicine; Attending Neonatologist, Neonatal ICU, UCI Medical Center and St Francis Medical Center

Fayez M Bany-Mohammed, MD is a member of the following medical societies: American Academy of Pediatrics, California Association of Neonatologists

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Arun K Pramanik, MD, MBBS Professor of Pediatrics, Louisiana State University Health Sciences Center

Arun K Pramanik, MD, MBBS is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society, National Perinatal Association, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Ted Rosenkrantz, MD Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine

Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, Eastern Society for Pediatric Research, American Medical Association, Connecticut State Medical Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Michael P Sherman, MD, FAAP † Former Professor, Department of Child Health, University of Missouri-Columbia School of Medicine; Neonatologist, Women’s and Children’s Hospital; Professor Emeritus, Department of Pediatrics, University of California, Davis, School of Medicine

Michael P Sherman, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, American Thoracic Society, European Society for Paediatric Research, Pediatric Infectious Diseases Society, Perinatal Research Society, Society for Pediatric Research, Western Society for Pediatric Research

Disclosure: Nothing to disclose.

Katsufumi Otsuki, MD, PhD Associate Professor, Chief, Department of Obstetrics and Gynecology, Showa University Koto-Toyosu Hospital, Japan

Disclosure: Nothing to disclose.

Naomi F Lauriello, MD Associate Professor, Sidney Kimmel Medical College of Thomas Jefferson University; Associate Physician, NICU, Nemours duPont Pediatrics at Thomas Jefferson University Hospital

Naomi F Lauriello, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Acknowledgements

Research by the author, Michael Sherman, is supported by NIH grant R44 HD 057744 and a grant from the Gerber Foundation. The author appreciates the review of the manuscript undertaken by Jan Sherman, RN, NNP, PhD, and her helpful recommendations for improvement.

Terminology	Features and Comments
Isolated Maternal Fever (“Documented” fever)	Maternal oral temperature ≥39.0°C (≥102.2°F) on any one occasion is documented fever. If the oral temperature is between 38.0°C (100.4°F) and 39.0°C (102.2°F), repeat the measurement in 30 minutes; if the repeat value remains at least 38.0°C (≥100.4°F), it is documented fever.
Suspected Triple I	Fever without a clear source plus any of the following: Baseline fetal tachycardia (>160 beats per min for 10 min or longer, excluding accelerations, decelerations, and periods of marked variability) Maternal white blood cell count >15,000 per mm ³ in the absence of corticosteroids Definite purulent fluid from the cervical os
Confirmed Triple I	All of the above plus: Amniocentesis-proven infection through a positive Gram stain Low glucose level or positive amniotic fluid culture Placental pathology revealing diagnostic features of infection

Chorioamnionitis

Practice Essentials

Signs and symptoms

Diagnosis

Management

Background

Pathophysiology

Etiology

Epidemiology

United States data

International data

Race-, sex-, and age-related demographics

Prognosis

Maternal sequelae

Neonatal sequelae

Patient Education

References

Tables

Contributor Information and Disclosures

What would you like to print?